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1. Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study

Author: Juan F. Vázquez-Costa, María Branas-Pampillón, Julita Medina-Cantillo, Mónica Povedano, Inmaculada Pitarch-Castellano, Mercedes López-Lobato, Joaquín A. Fernández-Ramos, Miguel Lafuente-Hidalgo, Ricard Rojas-García, José M. Caballero-Caballero, Ignacio Málaga, Jesús Eirís-Puñal, Mencía De Lemus, María G. Cattinari, Rosana Cabello-Moruno, Paola Díaz-Abós, Victoria Sánchez-Menéndez, Pablo Rebollo, Jorge Maurino, and Marcos Madruga-Garrido
Subjects: Spinal muscular atrophy, Patients and caregivers, Outcome measures, Quality of life, Symptom assessment, Disease burden, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Introduction Outcome measures traditionally used in spinal muscular atrophy (SMA) clinical trials are inadequate to assess the full range of disease severity. The aim of this study was to assess the psychometric properties of a set of existing questionnaires and new items, gathering information on the impact of SMA from the patient and caregiver perspectives. Methods This was a multicenter, prospective, noninterventional study including patients with a confirmed diagnosis of 5q-autosomal-recessive SMA aged 8 years and above, or their parents (if aged between 2 and 8 years). The set of outcome measurements included the SMA Independence Scale (SMAIS) patient and caregiver versions, the Neuro-QoL Fatigue Computer Adaptive Test (CAT), the Neuro-QoL Pain Short Form—Pediatric Pain, the PROMIS adult Pain Interference CAT, and new items developed by Fundación Atrofia Muscular España: perceived fatigability, breathing and voice, sleep and rest, and vulnerability. Reliability, construct validity, discriminant validity, and sensitivity to change (4 months from baseline) were measured. Results A total of 113 patients were included (59.3% 2–17 years old, 59.3% male, and 50.4% with SMA type II). Patients required moderate assistance [mean patient and caregiver SMAIS (SD) scores were 31.1 (12.8) and 7.6 (11.1), respectively]. Perceived fatigability was the most impacted domain, followed by vulnerability. Cronbach’s alpha coefficient for perceived fatigability, breathing and voice, and vulnerability total scores were 0.92, 0.88, and 0.85, respectively. The exploratory factor analysis identified the main factors considered in the design, except in the sleep and rest domain. All questionnaires were able to discriminate between the Clinical Global Impression—Severity scores and SMA types. Sensitivity to change was only found for the SMAIS caregiver version and vulnerability items. Conclusions This set of outcome measures showed adequate reliability, construct validity, and discriminant validity and may constitute a valuable option to measure symptom severity in patients with SMA.
Published: 2022
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2. Pain in Children and Adolescents with Spinal Muscular Atrophy: A Longitudinal Study from a Patient Registry

Author: Inmaculada Pitarch-Castellano, David Hervás, Maria Grazia Cattinari, Eugenia Ibáñez Albert, Mercedes López Lobato, Nancy Carolina Ñungo Garzón, Juan Rojas, Cristina Puig-Ram, and Marcos Madruga-Garrido
Subjects: pain, spinal muscular atrophy, neuromuscular disease, children, adolescent natural history, patient registry, Pediatrics, RJ1-570
Abstract: Spinal muscular atrophy (SMA) is a devastating genetic neurodegenerative disease caused by the insufficient production of Survival Motor Neuron (SMN) protein. It presents different phenotypes with frequent contractures and dislocations, scoliosis, and pain. This study aims to report the prevalence and description of pain and how it affects daily life by analyzing a new ad hoc questionnaire. An observational study of patients under 18 years of age with SMA was conducted at two referral centers in Spain. Data were analyzed using a descriptive analysis and a Bayesian ordinal regression model to assess the association with clinical and demographic variables. Fifty-one individuals were included in this study, 27% of whom reported pain with a median duration of 5.2 years and a mean Visual Analogic Scale (VAS) score of 5. Notably, 77% were receiving disease-modifying treatment, with more than 50% receiving analgesic treatment. The Bayesian model showed that functional status, lower limb contractures, and number of visits have a high probability (>90%) of influencing pain. Thus, the prevalence of pain in the SMA population under 18 years is substantial, and its presence could be associated with lower limb contractures, better functional status, and higher RULM (Revised Upper Limb Module) scores.
Published: 2023
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3. Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency

Author: Cristina Domínguez-González, Marcos Madruga-Garrido, Michio Hirano, Itxaso Martí, Miguel A. Martín, Francina Munell, Andrés Nascimento, Montse Olivé, Joanne Quan, M. Dolores Sardina, Ramon Martí, and Carmen Paradas
Subjects: Mitochondrial disease, Mitochondrial medicine, Thymidine kinase 2 deficiency (TK2d), Medicine
Abstract: Abstract Background Mitochondrial diseases are difficult to diagnose and treat. Recent advances in genetic diagnostics and more effective treatment options can improve patient diagnosis and prognosis, but patients with mitochondrial disease typically experience delays in diagnosis and treatment. Here, we describe a unique collaborative practice model among physicians and scientists in Spain focused on identifying TK2 deficiency (TK2d), an ultra-rare mitochondrial DNA depletion and deletions syndrome. Main Body This collaboration spans research and clinical care, including laboratory scientists, adult and pediatric neuromuscular clinicians, geneticists, and pathologists, and has resulted in diagnosis and consolidation of care for patients with TK2d. The incidence of TK2d is not known; however, the first clinical cases of TK2d were reported in 2001, and only ~ 107 unique cases had been reported as of 2018. This unique collaboration in Spain has led to the diagnosis of more than 30 patients with genetically confirmed TK2d across different regions of the country. Research affiliate centers have led investigative treatment with nucleosides based on understanding of TK2d clinical manifestations and disease mechanisms, which resulted in successful treatment of a TK2d mouse model with nucleotide therapy in 2010. Only 1 year later, this collaboration enabled rapid adoption of treatment with pyrimidine nucleotides (and later, nucleosides) under compassionate use. Success in TK2d diagnosis and treatment in Spain is attributable to two important factors: Spain’s fully public national healthcare system, and the designation in 2015 of major National Reference Centers for Neuromuscular Disorders (CSURs). CSUR networking and dissemination facilitated development of a collaborative care network for TK2d disease, wherein participants share information and protocols to request approval from the Ministry of Health to initiate nucleoside therapy. Data have recently been collected in a retrospective study conducted under a Good Clinical Practice–compliant protocol to support development of a new therapeutic approach for TK2d, a progressive disease with no approved therapies. Conclusions The Spanish experience in diagnosis and treatment of TK2d is a model for the diagnosis and development of new treatments for very rare diseases within an existing healthcare system.
Published: 2021
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4. Synaptic processes and immune-related pathways implicated in Tourette syndrome

Author: Fotis Tsetsos, Dongmei Yu, Jae Hoon Sul, Alden Y. Huang, Cornelia Illmann, Lisa Osiecki, Sabrina M. Darrow, Matthew E. Hirschtritt, Erica Greenberg, Kirsten R. Muller-Vahl, Manfred Stuhrmann, Yves Dion, Guy A. Rouleau, Harald Aschauer, Mara Stamenkovic, Monika Schlögelhofer, Paul Sandor, Cathy L. Barr, Marco A. Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Anke Hinney, Robert A. King, Thomas V. Fernandez, Csaba Barta, Zsanett Tarnok, Peter Nagy, Christel Depienne, Yulia Worbe, Andreas Hartmann, Cathy L. Budman, Renata Rizzo, Gholson J. Lyon, William M. McMahon, James R. Batterson, Danielle C. Cath, Irene A. Malaty, Michael S. Okun, Cheston Berlin, Douglas W. Woods, Paul C. Lee, Joseph Jankovic, Mary M. Robertson, Donald L. Gilbert, Lawrence W. Brown, Barbara J. Coffey, Andrea Dietrich, Pieter J. Hoekstra, Samuel Kuperman, Samuel H. Zinner, Michael Wagner, James A. Knowles, A. Jeremy Willsey, Jay A. Tischfield, Gary A. Heiman, Nancy J. Cox, Nelson B. Freimer, Benjamin M. Neale, Lea K. Davis, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Peristera Paschou, on behalf of the Tourette Association of America International Consortium for Genetics, Sabrina Darrow, Roger Kurlan, James F. Leckman, Jan H. Smit, the Gilles de la Tourette GWAS Replication Initiative, Harald Aschauer Harald Aschauer, Anastasios Konstantinidis, Kirsten Müller-Vahl, Tomasz Wolanczyk, the Tourette International Collaborative Genetics Study, Lawrence Brown, Keun-Ah Cheon, Blanca Garcia-Delgar, Donald Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Bennett L. Leventhal, Marcos Madruga-Garrido, Pablo Mir, Astrid Morer, Alexander Münchau, Kerstin J. Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Samuel Zinner, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group, Thomas Fernandez, Gary Heiman, Pieter Hoekstra, Jay Tischfield, and Douglas Woods
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
Published: 2021
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5. Desmin Modulates Muscle Cell Adhesion and Migration

Author: Coralie Hakibilen, Florence Delort, Marie-Thérèse Daher, Pierre Joanne, Eva Cabet, Olivier Cardoso, Fany Bourgois-Rocha, Cuixia Tian, Eloy Rivas, Marcos Madruga, Ana Ferreiro, Alain Lilienbaum, Patrick Vicart, Onnik Agbulut, Sylvie Hénon, and Sabrina Batonnet-Pichon
Subjects: desmin, vinculin, focal adhesion, migration, myopathies, intermediate filaments, Biology (General), QH301-705.5
Abstract: Cellular adhesion and migration are key functions that are disrupted in numerous diseases. We report that desmin, a type-III muscle-specific intermediate filament, is a novel cell adhesion regulator. Expression of p.R406W mutant desmin, identified in patients with desmin-related myopathy, modified focal adhesion area and expression of adhesion-signaling genes in myogenic C2C12 cells. Satellite cells extracted from desmin-knock-out (DesKO) and desmin-knock-in-p.R405W (DesKI-R405W) mice were less adhesive and migrated faster than those from wild-type mice. Moreover, we observed mislocalized and aggregated vinculin, a key component of cell adhesion, in DesKO and DesKI-R405W muscles. Vinculin expression was also increased in desmin-related myopathy patient muscles. Together, our results establish a novel role for desmin in cell-matrix adhesion, an essential process for strength transmission, satellite cell migration and muscle regeneration. Our study links the patho-physiological mechanisms of desminopathies to adhesion/migration defects, and may lead to new cellular targets for novel therapeutic approaches.
Published: 2022
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6. NOVEL intronic CAPN3 Roma mutation alters splicing causing RNA mediated decay

Author: Fabiola Mavillard, Marcos Madruga‐Garrido, Eloy Rivas, Emilia Servián‐Morilla, Rainiero Ávila‐Polo, Irene Marcos, Francisco J. Morón, Carmen Paradas, and Macarena Cabrera‐Serrano
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract CAPN3 mutations cause a limb girdle muscular dystrophy. Functional characterization of novel mutations facilitates diagnosis of future cases. We have identified a novel (c.1992 + 2T>G) CAPN3 mutation that disrupts the donor splice site of intron 17 splicing out exon 17, with mRNA levels severely reduced or undetectable. The mutation induces a strong change in the 3D structure of the mRNA which supports no‐go mRNA decay as the probable mechanism for RNA degradation. The mutation was identified in two unrelated Roma individuals showing a common ancestral origin and founder effect. This is the first Roma CAPN3 mutation to be reported.
Published: 2019
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7. Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study

Author: Martina Haas, Ewgeni Jakubovski, Carolin Fremer, Andrea Dietrich, Pieter J. Hoekstra, Burkard Jäger, Kirsten R. Müller-Vahl, The EMTICS Collaborative Group, Alan Apter, Valentina Baglioni, Juliane Ball, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Judith Buse, Francesco Cardona, Marta Correa Vela, Nanette M. Debes, Maria Cristina Ferro, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Chaim Huyser, Marcos Madruga-Garrido, Anna Marotta, Davide Martino, Pablo Mir, Astrid Morer, Norbert Müller, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Alessandra Pellico, Ángela Periañez Vasco, Kerstin J. Plessen, Cesare Porcelli, Marina Redondo, Renata Rizzo, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Anette Schrag, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok, Jennifer Tübing, Victoria L. Turner, Susanne Walitza, and Elif Weidinger
Subjects: Tourette's syndrome (TS), YGTSS = Yale Global Tic Severity Scale, psychometric properties, internal consistency, confirmatory factor analysis, Psychiatry, RC435-571
Abstract: The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale “European Multicentre Tics in Children Study” (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (rs = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (rs = 0.24), obsessive–compulsive symptoms (rs = 27) as well as internalizing symptoms (rs = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors “motor tics” and “phonic tics,” but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial.
Published: 2021
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8. Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

Author: Marcio Andrade-Campos, Pilar Alfonso, Pilar Irun, Judith Armstrong, Carmen Calvo, Jaime Dalmau, Maria-Rosario Domingo, Jose-Luis Barbera, Horacio Cano, Maria-Angeles Fernandez-Galán, Rafael Franco, Inmaculada Gracia, Miguel Gracia-Antequera, Angela Ibañez, Francisco Lendinez, Marcos Madruga, Elena Martin-Hernández, Maria del Mar O’Callaghan, Alberto Pérez del Soto, Yolanda Ruiz del Prado, Ignacio Sancho-Val, Pablo Sanjurjo, Miguel Pocovi, and Pilar Giraldo
Subjects: Children, Gaucher Disease, Enzymatic replacement therapy, Medicine
Abstract: Abstract Background The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Aim To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Methods A review of data in SpRGD from patients’ diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B). Results A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17–16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p
Published: 2017
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9. Investigation of gene-environment interactions in relation to tic severity

Author: Frank Visscher, Kerstin J. Plessen, Tammy Hedderly, Jungeun Song, Bennett L. Leventhal, Eun-Young Shin, Lawrence W. Brown, Alexander Münchau, Robert A. King, Young Key Kim, Young Shin Kim, Veit Roessner, Andrea Dietrich, Samuel Kuperman, Thomas V. Fernandez, Keun-Ah Cheon, Carol A. Mathews, Athanasios Maras, Donald L. Gilbert, Yun-Joo Koh, Laura Ibanez-Gomez, Dongmei Yu, Astrid Morer, Sodahm Kook, Marcos Madruga-Garrido, Julie Hagstrøm, Dorothy E. Grice, Jay A. Tischfield, Lisa Osiecki, Mohamed Abdulkadir, Blanca Garcia-Delgar, Samuel H. Zinner, Chaim Huyser, Barbara J. Coffey, Dong-Ho Song, Gary A. Heiman, Pieter J. Hoekstra, Hyun Ju Hong, Pablo Mir, Isobel Heyman, Jeremiah M. Scharf, National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, Judah Foundation, Tourette Association of America, National Institutes of Health (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Generalitat de Catalunya, German Research Foundation, National Institute of Environmental Health Sciences (US), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Paediatric Psychosocial Care, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Subjects: Candidate gene, Tic severity, Autism Spectrum Disorder, Autism, Intellectual and Developmental Disabilities (IDD), Single-nucleotide polymorphism, Genome-wide association study, Neurodegenerative, Tourette syndrome, Severity of Illness Index, Attention Deficit Disorder with Hyperactivity/genetics, Autism Spectrum Disorder/genetics, Female, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Pregnancy, Tics, Tourette Syndrome, Gene–environment interaction, Pre- and perinatal complications, mental disorders, medicine, Genetics, SNP, 2.1 Biological and endogenous factors, Psychology, Aetiology, Biological Psychiatry, Genetic association, Pediatric, Neurology & Neurosurgery, business.industry, Psychiatry and Preclinical Psychiatric Studies - Original Article, Human Genome, Neurosciences, medicine.disease, Serious Mental Illness, Gene-environment interaction, Brain Disorders, Psychiatry and Mental health, Mental Health, Neurology, Autism spectrum disorder, Attention Deficit Disorder with Hyperactivity, Neurology (clinical), business
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies., This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462).
Published: 2021
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10. Vanishing White Matter Disease in a Spanish Population

Author: Eulàlia Turón-Viñas, Mercè Pineda, Victòria Cusí, Eduardo López-Laso, Rebeca Losada del Pozo, Luis González Gutiérrez-Solana, David Conejo Moreno, Concha Sierra-Córcoles, Naiara Olabarrieta-Hoyos, Marcos Madruga-Garrido, Javier Aguirre-Rodríguez, Verónica González-Álvarez, Mar O’Callaghan, Jordi Muchart, and Judith Armstrong-Moron
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2014

11. Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

Author: Molly, Bond, Natalie, Moll, Alicia, Rosello, Rod, Bond, Jaana, Schnell, Bianka, Burger, Pieter, J Hoekstra, Andrea, Dietrich, Anette, Schrag, Eva, Kocovska, Martino, Davide, Norbert, Mueller, Markus, Schwarz, Ute-Christiane, Meier, EMTICS Collaborative Group: Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Anna, Marotta, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, R Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Kerstin, J Plessen, Cesare, Porcelli, Marina, Redondo, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana Ml Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Jennifer, Tübing, Victoria, L Turner, Susanne, Walitza, Elif, Weidinger, Clinical Cognitive Neuropsychiatry Research Program (CCNP), EMTICS Collaborative Group, Bruun, J.E., Grejsen, J., Ommundsen, C.L., Rubæk, M., Enghardt, S., Bokemeyer, S., Driedger-Garbe, C., Reichert, C., Schmalfeld, J., Duffield, T., Gergye, F., Kovacs, M., Vidomusz, R., Carmel, M., Fennig, S., Gev, E., Keller, N., Michaelovsky, E., Nahon, M., Regev, C., Simcha, T., Smollan, G., Weizman, A., Gagliardi, G., Tallon, M., Roazzi, P., van den Ban, E., de Bruijn, SFTM, Driessen, N., Lamerz, A., Messchendorp, M., Rath, JJG, Sival, NSD, Tromp, N., Visscher, F., de la Tourettes, S.G., Cáceres, M.T., Carrillo, F., Gómez-Garre, P., Vargas, L., Gariup, M., Stöber, S., Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bond, M., Bognar, E., Burger, B., Buse, J., Cardona, F., Vela, M.C., Dietrich, A., Debes, N.M., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Madruga-Garrido, M., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Mueller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Vasco, Á.P., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Gloor, F.T., Tarnok, Z., Tübing, J., Turner, V.L., Walitza, S., Weidinger, E., and Woods, M.L.
Subjects: Obsessive-Compulsive Disorder, Tic disorder, medicine.medical_specialty, Adolescent, Tics, Comorbidity, Severity of Illness Index, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Vitamin D and neurology, Humans, ADHD, Vitamin D, Child, OCD, business.industry, Tourette, Symptom severity, General Medicine, Attention Deficit Disorder with Hyperactivity/psychology, Cross-Sectional Studies, Obsessive-Compulsive Disorder/epidemiology, Obsessive-Compulsive Disorder/psychology, Tic Disorders/metabolism, Tic Disorders/psychology, Tics/complications, Tics/metabolism, Tourette Syndrome/psychology, Vitamin D/metabolism, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Cohort, CTD, business, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p
Published: 2022

12. Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group

Author: Blanca, Garcia‐delgar, Mateu, Servera, Coffey, Barbara J., Luisa, Lázaro, Thaïra, Openneer, Noa, Benaroya‐milshtein, Tami, Steinberg, Hoekstra, Pieter J., Andrea, Dietrich, Astrid Morer EMTICS collaborative group Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Debes, Nanette M., Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Hedderly, Tammy J., Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Anna, Marotta, Martino, Davide, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Openneer, Thaïra J. C., Pellico, Alessandra, Plessen, Kerstin J., Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Schnell, Jaana M. L., Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Susanne Walitza &amp, Elif, Weidinger, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, and ANS - Cellular & Molecular Mechanisms
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Younger age, Tics, Adolescent, Autism Spectrum Disorder, Comorbidity, Adolescents, Tourette syndrome, Severity of Illness Index, Limited access, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Sex differences, Developmental and Educational Psychology, Child and adolescent psychiatry, Medicine, Humans, 0501 psychology and cognitive sciences, 10. No inequality, Child, Children, business.industry, 05 social sciences, General Medicine, medicine.disease, 030227 psychiatry, body regions, Psychiatry and Mental health, Autism spectrum disorder, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Female, Presentation (obstetrics), business, human activities, 050104 developmental & child psychology, Male predominance
Abstract: Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.
Published: 2022

13. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

Author: Anette-Eleonore, Schrag, Martino, Davide, Hanyuying, Wang, Gareth, Ambler, Noa, Benaroya-Milstein, Maura, Buttiglione, Cardona, Francesco Carmelo Giovanni, Roberta, Creti, Androulla, Efstratiou, Tammy, Hedderly, Isobel, Heyman, Chaim, Huyser, Pablo, Mir, Astrid, Morer, Natalie, Moll, Norbert, E Müller, Kirsten, R Müller-Vahl, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Markus, Schwarz, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Pieter, J Hoekstra Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Pieter, J Hoekstra, Marcos, Madruga-Garrido, Anna, Marotta, Norbert, Müller, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Marina, Redondo, Daphna, Ruhrman, Jaana Ml Schnell, Anette, Schrag, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Jennifer, Tübing, Victoria, L Turner, and Elif, Weidinger
Subjects: Neuroimmunity, Neuroinflammation, Tic Disorders, Streptococcal infections
Published: 2022

14. Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders

Author: Martino, Davide, Anette, Schrag, Zacharias, Anastasiou, Alan, Apter, Noa, Benaroya-Milstein, Maura, Buttiglione, Cardona, Francesco Carmelo Giovanni, Roberta, Creti, Androulla, Efstratiou, Tammy, Hedderly, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Kirsten Mu ̈ller-Vahl, Alexander, Munchau, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Jaana, Schnell, Markus, Schwarz, Liselotte, Skov, Tamar, Steinberg, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Hoekstra, Pieter J., Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Friederike Tagwerker Gloor, and Susanne Walitza, Elif Weidinger
Subjects: neuroimmunity, Tourette syndrome, tic disorders, neuroimmunity, tic disorders
Published: 2021

15. Clinical precursors of tics: an EMTICS study

Author: Openneer, Tha€ıra J. C., Chaim, Huyser, Martino, Davide, Anette, Schrag, Alan, Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Nanette, M Debes, Andrea, Dietrich, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Isobel, Heyman, Marcos, Madruga-Garrido, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Susanne, Walitza, Elif, Weidinger, Hoekstra, Pieter J., Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, ANS - Cellular & Molecular Mechanisms, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Male, sex differences, Pediatrics, Longitudinal study, SYMPTOMS, Autism Spectrum Disorder, Comorbidity, Logistic regression, Tourette syndrome, 0302 clinical medicine, Developmental and Educational Psychology, Obsessive compulsive scale, Spectrum disorder, Longitudinal Studies, Child, 05 social sciences, PSYCHIATRIC-DISORDERS, clinical precursors, PREVALENCE, Psychiatry and Mental health, Autism spectrum disorder, Child, Preschool, Compulsions, Tics, Female, Psychology, 050104 developmental & child psychology, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, conduct problems, 03 medical and health sciences, OBSESSIVE-COMPULSIVE SCALE, mental disorders, medicine, Humans, ADHD, 0501 psychology and cognitive sciences, tic onset, SPECTRUM DISORDER, TOURETTE-SYNDROME, medicine.disease, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, SEVERITY, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Selection operator, human activities, 030217 neurology & neurosurgery, DISRUPTIVE BEHAVIOR, Tourette Syndrome
Abstract: Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics.Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample.Results: Children with tic onset were more frequently male (beta = -0.36), had higher baseline severity of conduct problems (beta = 0.23), autism spectrum disorder symptoms (ASD; beta = 0.08), compulsions (beta = 0.02) and emotional problems (beta = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (beta = 0.39) and emotional problems were female-specific predictors.Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient.
Published: 2021

16. Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder

Author: Xiao Fan, Donnielle Rome-Martin, Elizabeth Poole-Di Salvo, Gabriela Soares, Cynthia G. Keator, Cheryl Pan, Marcos Madruga-Garrido, Francesca Novara, Jennifer M. Bain, Lia Boyle, Steven A. Skinner, Karen Y. Niederhoffer, Richard Frye, Nicole M. LaMarca, Silke Hamp, Orrin Devinsky, Wendy K. Chung, Rachel Salazar, Sylvie Goldman, Alexis B.R. Maddocks, Angela Peron, and Olivia Thornburg
Subjects: 0301 basic medicine, medicine.medical_specialty, Pediatrics, Cortical visual impairment, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, medicine, Genetics (clinical), Exome sequencing, Molecular pathology, business.industry, medicine.disease, 030104 developmental biology, Autism spectrum disorder, Medical genetics, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: ObjectiveTo expand the clinical phenotype of the X-linked HNRNPH2-related neurodevelopmental disorder in 33 individuals.MethodsParticipants were diagnosed with pathogenic or likely pathogenic variants in HNRNPH2 using American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria, largely identified via clinical exome sequencing. Genetic reports were reviewed. Clinical data were collected by retrospective chart review and caregiver report including standardized parent report measures.ResultsWe expand our clinical characterization of HNRNPH2-related disorders to include 33 individuals, aged 2–38 years, both females and males, with 11 different de novo missense variants, most within the nuclear localization signal. The major features of the phenotype include developmental delay/intellectual disability, severe language impairment, motor problems, growth, and musculoskeletal disturbances. Minor features include dysmorphic features, epilepsy, neuropsychiatric diagnoses such as autism spectrum disorder, and cortical visual impairment. Although rare, we report early stroke and premature death with this condition.ConclusionsThe spectrum of X-linked HNRNPH2-related disorders continues to expand as the allelic spectrum and identification of affected males increases.
Published: 2021

17. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy

Author: C. Jimenez-Mallebrera, Cristina Domínguez-González, Selena Trifunov, Jordi Díaz-Manera, Carmen Badosa, Fabiola Mavillard, Julio Montoya, Itxaso Marti, Michio Hirano, Marcos Madruga-Garrido, Carmen Paradas, Raquel Montero, Daniel Cuadras, Rafael Artuch, Ramon Martí, Jorge Alonso-Pérez, Joan Villarroya, Andres Berardo, Susana G. Kalko, Yolanda Cámara, Miguel A. Martín, Andrés Nascimento, Eduardo Ruiz-Pesini, Carlos Ortez, Cora Blázquez-Bermejo, Francesc Villarroya, Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Muscular Dystrophy Association (US), and Arturo Estopinan TK2 Research Fund
Subjects: 0301 basic medicine, Male, Mitochondrial Diseases, lcsh:Medicine, Diseases, Gastroenterology, Mitocondris, Basal (phylogenetics), 0302 clinical medicine, Medicine, lcsh:Science, Child, Multidisciplinary, Biochemical markers, Middle Aged, Prognosis, Mitochondria, Neurology, Child, Preschool, Marcadors bioquímics, embryonic structures, Biomarker (medicine), Female, medicine.symptom, After treatment, Adult, medicine.medical_specialty, Growth Differentiation Factor 15, DNA, Mitochondrial, Thymidine Kinase, Article, 03 medical and health sciences, Disease severity, Muscular Diseases, Internal medicine, Genetics, Humans, In patient, Myopathy, Muscle, Skeletal, Aged, business.industry, lcsh:R, Infant, Fibroblast Growth Factors, 030104 developmental biology, Potential biomarkers, lcsh:Q, GDF15, business, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract: GDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1–49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age., This work was supported by research grants of Plan Nacional de I + D + I and Instituto de Salud Carlos III (ISCIII), Subdirección General de Evaluación y Fomento de la Investigación Sanitaria, projects PI16/01843 (CP), PI16/00579 and CP09/00011 (CJM), PI15/00431 (MAM), PI17/00109 (RA) and PI18/01574 (RM), co-funded with European Regional Development Fund (ERDF) “A way to achieve Europe”; multicentric grant funded by the ISCIII (PMP15/00025, MAM, RM, CP), Grants of the Ministerio de Ciencia, Innovación y Universidades SAF2017-85722 (FV) and SAF2017-87506-R (YC), the Muscular Dystrophy Association grant 577391 (MH), and the Arturo Estopinan TK2 Research Fund (MH).
Published: 2020

18. European Multicentre Tics in Children Studies (EMTICS)

Author: Schrag, A, Martino, D, Apter, A, Ball, J, Bartolini, E, Benaroya-Milshtein, N, Buttiglione, M, Cardona, F, Creti, R, Efstratiou, A, Gariup, M, Georgitsi, M, Hedderly, T, Heyman, I, Margarit, I, Mir, P, Moll, N, Morer, A, Müller, N, Müller-Vahl, K, Münchau, A, Orefici, G, Plessen, Kj, Porcelli, C, Paschou, P, Rizzo, R, Roessner, V, Schwarz, Mj, Steinberg, T, Tagwerker Gloor, F, Tarnok, Z, Walitza, S, Dietrich, A, Hoekstra, Pj, Zacharias, Anastasiou, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Renata, Rizzo, Veit, Roessner, Jaana, Schnell, Liselotte, Skov, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Tamar, Steinberg, Friederike Tagwerker Gloor, Elif, Weidinger, EMTICS Collaborative Group, Anastasiou, Z., Apter, A., Baglioni, V., Ball, J., Bartolini, E., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Buttiglione, M., Cardona, F., Correa Vela, M., Creti, R., Dietrich, A., Debes, N.M., Efstratiou, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gariup, M., Georgitsi, M., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Imperi, M., Karagiannidis, I., Laviola, G., Macri, S., Madruga-Garrido, M., Margarit, I., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Orefici, G., Paschou, P., Pellico, A., Petruzzelli, O., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roazzi, P., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schütze, G.A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Stöber, S., Gloor, F.T., Tallon, M., Tarnok, Z., Turner, V.L., Walitza, S., Weidinger, E., Woods, M.L., European Commission, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), University College London, NHS Foundation Trust, GlaxoSmithKline, German Research Foundation, Instituto de Biomedicina de Sevilla (IBIS), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Male, Pediatrics, Tic disorder, BLOOD, Tourette syndrome, Obsessive–compulsive disorder, Cohort Studies, 0302 clinical medicine, Risk Factors, QUALITY-OF-LIFE, Obsessive-compulsive disorder, Developmental and Educational Psychology, Genetics, Longitudinal, Streptococcal infection, Stress, Prospective cohort study, Child, GENE-EXPRESSION, education.field_of_study, HAIR CORTISOL, 05 social sciences, A STREPTOCOCCAL INFECTIONS, Original Contribution, General Medicine, 3. Good health, Europe, Psychiatry and Mental health, LA-TOURETTE SYNDROME, Child, Preschool, NEUROPSYCHIATRIC DISORDERS, Cohort, Female, 050104 developmental & child psychology, Cohort study, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Tics, Adolescent, PSYCHOSOCIAL STRESS, Population, 03 medical and health sciences, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Genetic Predisposition to Disease, education, Tic Disorders/complications, Tic Disorders/diagnosis, Tic Disorders/pathology, business.industry, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, 030227 psychiatry, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, business, human activities
Abstract: EMTICS Collaborative Group., Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 278367. Schrag was supported by the National Institute for Health Research UCLH Biomedical Research Centre, and Müller, Burger, Schnell and Weidinger by Stiftung Immunität und Seele. This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (Heyman); partially sponsored by GSK Vaccines (Margarit, Bartolini); and Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1 (Münchau).
Published: 2019
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19. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Sheng Wang, Jeffrey D. Mandell, Yogesh Kumar, Nawei Sun, Montana T. Morris, Juan Arbelaez, Cara Nasello, Shan Dong, Clif Duhn, Xin Zhao, Zhiyu Yang, Shanmukha S. Padmanabhuni, Dongmei Yu, Robert A. King, Andrea Dietrich, Najah Khalifa, Niklas Dahl, Alden Y. Huang, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Thomas V. Fernandez, Joseph D. Buxbaum, Silvia De Rubeis, Dorothy E. Grice, Jinchuan Xing, Gary A. Heiman, Jay A. Tischfield, Peristera Paschou, A. Jeremy Willsey, Matthew W. State, Mohamed Abdulkadir, Benjamin Bodmer, Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Lonneke Elzerman, Carolin Fremer, Blanca Garcia-Delgar, Donald L. Gilbert, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Pieter J. Hoekstra, Hyun Ju Hong, Chaim Huyser, Eun-Joo Kim, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett L Leventhal, Andrea G. Ludolph, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Montana T Morris, Kirsten Müller-Vahl, Alexander Münchau, Tara L. Murphy, Kerstin J. Plessen, Hannah Poisner, Veit Roessner, Stephan J. Sanders, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Joshua K. Thackray, Jennifer Tübing, Frank Visscher, Sina Wanderer, A Jeremy Willsey, Martin Woods, Yeting Zhang, Samuel H. Zinner, Christos Androutsos, Csaba Barta, Luca Farkas, Jakub Fichna, Marianthi Georgitsi, Piotr Janik, Iordanis Karagiannidis, Anastasia Koumoula, Peter Nagy, Joanna Puchala, Renata Rizzo, Natalia Szejko, Urszula Szymanska, Zsanett Tarnok, Vaia Tsironi, Tomasz Wolanczyk, Cezary Zekanowski, Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Cornelia Illmann, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. MacMahon, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG), Abdulkadir, M., Arbelaez, J., Bodmer, B., Bromberg, Y., Brown, L.W., Cheon, K.A., Coffey, B.J., Deng, L., Dietrich, A., Dong, S., Duhn, C., Elzerman, L., Fernandez, T.V., Fremer, C., Garcia-Delgar, B., Gilbert, D.L., Grice, D.E., Hagstrøm, J., Hedderly, T., Heiman, G.A., Heyman, I., Hoekstra, P.J., Hong, H.J., Huyser, C., Kim, E.J., Kim, Y.K., Kim, Y.S., King, R.A., Koh, Y.J., Kook, S., Kuperman, S., Leventhal, B.L., Ludolph, A.G., Madruga-Garrido, M., Mandell, J.D., Maras, A., Mir, P., Morer, A., Morris, M.T., Müller-Vahl, K., Münchau, A., Murphy, T.L., Nasello, C., Plessen, K.J., Poisner, H., Roessner, V., Sanders, S.J., Shin, E.Y., Song, D.H., Song, J., State, M.W., Sun, N., Thackray, J.K., Tischfield, J.A., Tübing, J., Visscher, F., Wanderer, S., Wang, S., Willsey, A.J., Woods, M., Xing, J., Zhang, Y., Zhao, X., Zinner, S.H., Androutsos, C., Barta, C., Farkas, L., Fichna, J., Georgitsi, M., Janik, P., Karagiannidis, I., Koumoula, A., Nagy, P., Paschou, P., Puchala, J., Rizzo, R., Szejko, N., Szymanska, U., Tarnok, Z., Tsironi, V., Wolanczyk, T., Zekanowski, C., Barr, C.L., Batterson, J.R., Berlin, C., Bruun, R.D., Budman, C.L., Cath, D.C., Chouinard, S., Coppola, G., Cox, N.J., Darrow, S., Davis, L.K., Dion, Y., Freimer, N.B., Grados, M.A., Hirschtritt, M.E., Huang, A.Y., Illmann, C., Kurlan, R., Leckman, J.F., Lyon, G.J., Malaty, I.A., Mathews, C.A., MacMahon, W.M., Neale, B.M., Okun, M.S., Osiecki, L., Pauls, D.L., Posthuma, D., Ramensky, V., Robertson, M.M., Rouleau, G.A., Sandor, P., Scharf, J.M., Singer, H.S., Smit, J., Sul, J.H., and Yu, D.
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, DNA Copy Number Variations, Receptors, Cell Surface, Biology, Genome, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, RARE, SCHIZOPHRENIA, medicine, Humans, Copy-number variation, Child, NEURODEVELOPMENTAL DISORDERS, Gene, lcsh:QH301-705.5, Exome sequencing, 030304 developmental biology, Medicinsk genetik, Sequence (medicine), Genetics, 0303 health sciences, SEVERE INTELLECTUAL DISABILITY, Cadherin, MUTATIONS, AUTISM SPECTRUM DISORDER, Cell Polarity, OBSESSIVE-COMPULSIVE DISORDER, Cadherins, medicine.disease, Pedigree, PREVALENCE, CONGENITAL HEART-DISEASE, GENOME, 030104 developmental biology, lcsh:Biology (General), Schizophrenia, Medical genetics, Female, Cadherins/genetics, Receptors, Cell Surface/genetics, Tourette Syndrome/genetics, Tourette Syndrome/pathology, TIC Genetics, Tourette disorder, cell polarity, copy number variants, de novo variants, gene discovery, microarray genotyping, multiplex, simplex, whole exome sequencing, Medical Genetics, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: SUMMARY We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk., In Brief Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis., Graphical Abstract
Published: 2018

20. Investigation of previously implicated genetic variants in chronic tic disorders

Author: Samuel Kuperman, Frank Visscher, Kirsten R. Müller-Vahl, Eun-Young Shin, Jennifer Tübing, Els van den Ban, Sina Wanderer, Hyun Ju Hong, Yun-Joo Koh, Jungeun Song, Gary A. Heiman, Lonneke Elzerman, Donald L. Gilbert, Derek Gordon, Laura Ibanez-Gomez, Keun-Ah Cheon, Douglas Londono, Young Key Kim, Bennett L. Leventhal, Alexander Münchau, Odette Fründt, Andrea G. Ludolph, Astrid Morer, Sodahm Kook, Thomas V. Fernandez, Lawrence W. Brown, Marcos Madruga-Garrido, Ewgeni Jakubovski, Jay A. Tischfield, Mohamed Abdulkadir, Blanca Garcia-Delgar, Carolin Fremer, Samuel H. Zinner, Pablo Mir, Robert A. King, Martin Woods, Veit Roessner, Young Shin Kim, Isobel Heyman, Tara Murphy, Athanasios Maras, Dong-Ho Song, Pieter J. Hoekstra, Tammy Hedderly, Barbara J. Coffey, Andrea Dietrich, Chaim Huyser, Dorothy E. Grice, Kerstin J. Plessen, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, and Child and Adolescent Psychiatry / Psychology
Subjects: 0301 basic medicine, Male, Candidate gene, Genome-wide association study, Tryptophan Hydroxylase, Obsessive–compulsive disorder, Severity of Illness Index, Linkage Disequilibrium, PICALM, 0302 clinical medicine, Candidate gene study, Obsessive-compulsive disorder, Pharmacology (medical), Child, POPULATION, Psychiatry, Genetics, LA-TOURETTE-SYNDROME, education.field_of_study, SLITRK1 GENE, Single Nucleotide, General Medicine, Transmission disequilibrium test, Middle Aged, 3. Good health, Psychiatry and Mental health, COMPREHENSIVE METAANALYSIS, Child, Preschool, HISTIDINE-DECARBOXYLASE, Cognitive Sciences, Female, Microtubule-Associated Proteins, Adult, Adolescent, Genotype, Clinical Sciences, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, SNP, Humans, Polymorphism, GENOME-WIDE ASSOCIATION, AUTISM, Preschool, education, Biological Psychiatry, FAMILY-BASED ASSOCIATION, Genetic association, Family Health, Original Paper, Tourette syndrome, Neurosciences, OBSESSIVE-COMPULSIVE DISORDER, Transmission Disequilibrium Test, CROSS-DISORDER, 030104 developmental biology, Attention-deficit/hyperactivity disorder, Tic Disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes. Electronic supplementary material The online version of this article (doi:10.1007/s00406-017-0808-8) contains supplementary material, which is available to authorized users.
Published: 2018
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21. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy

Author: Francisco Javier Aguirre‐Rodríguez, Susana G. Kalko, Elena Martín-Hernández, Fabiola Mavillard, Michio Hirano, Javier Torres-Torronteras, Bruce Levin, Marcos Madruga-Garrido, Cecilia Jimenez-Mallebrera, Yuqi Tu, Juan P. Morealejo‐Aycinena, Yuelin Long, Karin Kleinsteuber, Ramon Martí, Itxaso Marti, Jasim Uddin, Olga Serrano, Caterina Garone, Concepcion Álvarez del Vayo, M. Alice Donati, Francina Munell, John L.P. Thompson, Carmen Paradas, Cristina Domínguez-González, Andrés Nascimento, M. Dolores Sardina, Kristen Engelstad, Dominguez-Gonzalez C., Madruga-Garrido M., Mavillard F., Garone C., Aguirre-Rodriguez F.J., Donati M.A., Kleinsteuber K., Marti I., Martin-Hernandez E., Morealejo-Aycinena J.P., Munell F., Nascimento A., Kalko S.G., Sardina M.D., Alvarez del Vayo C., Serrano O., Long Y., Tu Y., Levin B., Thompson J.L.P., Engelstad K., Uddin J., Torres-Torronteras J., Jimenez-Mallebrera C., Marti R., Paradas C., Hirano M., Instituto de Salud Carlos III, Generalitat de Catalunya, European Commission, Muscular Dystrophy Association (US), and Arturo Estopinan TK2 Research Fund
Subjects: 0301 basic medicine, Adult, Compassionate Use Trials, Male, medicine.medical_specialty, Neurology, Side effect, medicine.medical_treatment, Deoxyribonucleosides, Walk Test, Gastroenterology, Thymidine Kinase, Article, 03 medical and health sciences, 0302 clinical medicine, Muscular Diseases, Internal medicine, tk2, myopathy, nucleosides, therapy, medicine, Humans, Myopathy, Child, Feeding tube, Mechanical ventilation, business.industry, Discontinuation, Diarrhea, 030104 developmental biology, Child, Preschool, Female, Neurology (clinical), GDF15, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: [Objective] Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies., [Methods] We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2‐deficient patients under a compassionate use program., [Results] In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6‐minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose‐dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy., [Interpretation] This open‐label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293–303, This work was supported in part by grants from the Spanish Carlos III Health Institute (PMP15/00025 for C.P., F.Ma., and R.M.; PI16/00579 and CP09/00011 for C.J.‐M.), Muscular Dystrophy Association (577391), Arturo Estopinan TK2 Research Fund, Generalitat de Catalunya PERIS program (SLT002/16/00370 for J.T‐T.), and European Regional Development Fund.
Published: 2019

22. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author: Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. Davis, Lenka Slachtova, Olav B. Smeland, Erin C. Dunn, Nicholas G. Martin, Allan L. Naarden, Jo Knight, Cristina Sánchez-Mora, Masashi Ikeda, Lorraine Southam, Sandro Sorbi, Barbara Franke, Martin Schalling, Russell Schachar, Yen-Chen Anne Feng, Kirsten R. Müller-Vahl, André Scherag, Zhaozhong Zhu, Eric A. Storch, Páll Magnússon, David Cohen, Olafur O Gudmundsson, Harvey S. Singer, Brian Kelly, Jonas Bybjerg-Grauholm, Blanca Garcia-Delgar, Thomas Hansen, Carmel M. Loughland, Christine Lochner, Stacy Steinberg, Martin Woods, Jorge A. Quiroz, Raquel Rabionet, Alden Y. Huang, Janice M. Fullerton, María Soler Artigas, Hans J. Grabe, Philip Asherson, Margit Burmeister, Alicia R. Martin, Martin A. Kennedy, Janet Treasure, Anders D. Børglum, Eva C. Schulte, Andreas Hartmann, Frans Henskens, Youl-Ri Kim, Jens Treutlein, Joanna Hauser, Manfred M. Fichter, Damiaan Denys, Ann E. Pulver, Kelly L. Klump, Paul Sandor, Michael Wagner, Philippe Courtet, Sandra Van der Auwera, Susanne Lucae, Eystein Stordal, Michel G. Nivard, Maurizio Clementi, Astrid Morer, Philip B. Mitchell, Huda Akil, Edwin H. Cook, Jennifer L. Moran, Donald W. Black, Jeremiah M. Scharf, Jana Strohmaier, Colm McDonald, Meg M.-J. Wang, Richard M. Myers, Stephanie Godard, Pablo V. Gejman, Athanasios Maras, Marcella Rietschel, Nancy G. Buccola, Konstantinos Hatzikotoulas, Dalila Pinto, Jouke-Jan Hottenga, Kari Stefansson, James S. Sutcliffe, Andres Metspalu, Amaia Hervás, Joel Gelernter, Wolfgang Herzog, Paula Rovira, Gunnar Morken, Tara Murphy, Mark Weiser, Vincent Millischer, Frank Dudbridge, Dan Rujescu, Vladimir Bencko, Valdo Ricca, Kimberly Chambert, Guy A. Rouleau, James J. Crowley, Thomas G. Schulze, Toni-Kim Clarke, Triinu Peters, Gudrun Wagner, Daniel A. Geller, Henry R. Kranzler, G. Bragi Walters, Vera Golimbet, Clement C. Zai, Nigel Williams, Andreas Birgegård, Joseph D. Buxbaum, Elliot M. Tucker-Drob, Jerome C. Foo, Tracey L. Petryshen, Daniel P. Howrigan, Hunna J. Watson, Franziska Degenhardt, Peter R. Schofield, Jesper Buchhave Poulsen, Stefan Herms, Johannes Hebebrand, Mario Maj, George Kirov, Fabrizio Piras, Sara McDevitt, James T. McCracken, Carol A. Mathews, Michael John Owen, Peter Falkai, Donald L. Gilbert, Enda M. Byrne, Fernando Fernández-Aranda, Csaba Barta, Stéphane Jamain, Jubao Duan, Dongmei Yu, Danielle C. Cath, Ole Mors, Sigrun Hope, Laramie E. Duncan, Alan R. Sanders, Sang-Yun Oh, Carsten Bøcker Pedersen, Henning Tiemeier, Roseann E. Peterson, Raymond K. Walters, Margarita C T Slof-Op 't Landt, Madeline Alexander, Stephanie Le Hellard, Ina Giegling, Annemarie A. van Elburg, Steven P. Hamilton, Vesna Boraska Perica, Thomas V. Fernandez, Danielle M. Dick, Francesco Bettella, Roel A. Ophoff, Grant W. Montgomery, Gerald Nestadt, Nakao Iwata, Jessica H. Baker, Walter H. Kaye, Jeremy M. Silverman, Mark J. Daly, Robert A. King, Sarah E. Medland, Anastasios Konstantinidis, Robert D. Oades, Samuel H. Zinner, Steven Crawford, Daniel H. Geschwind, Patrick W. L. Leung, Martin Alda, Marie Navratilova, Pak C. Sham, Paul A. Tooney, Tian Ge, Veit Roessner, Martin Preisig, Thomas Werge, Eli A. Stahl, David A. Collier, Stephanie H. Witt, Dermot Walsh, Miquel Casas, Anna Keski-Rahkonen, Jane H. Christensen, Silvia De Rubeis, Giorgio Pistis, Sven Cichon, Bruno Etain, Dominique Campion, O. Joseph Bienvenu, Christian Dina, Manolis Kogevinas, Thomas Espeseth, Benjamin M. Neale, Ditte Demontis, Klaus-Peter Lesch, Marina Mitjans, Tiffany A. Greenwood, Marcos Madruga-Garrido, Sibylle G. Schwab, Oedegaard Ketil Joachim, Hreinn Stefansson, Sara A. Paciga, Monica Forzan, Dieter B. Wildenauer, Lena Backlund, A. Jeremy Willsey, Carlos N. Pato, Nicholas John Craddock, Inge A. Meijer, Sandra K. Loo, Filip Rybakowski, Tracey D. Wade, Scott J. Crow, Bernard Lerer, Valsamma Eapen, Esben Agerbo, Andrew M. McIntosh, Luis Augusto Rohde, Susan L. McElroy, Stephan Zipfel, Peter P. Zandi, Cathryn M. Lewis, Lars Klareskog, Martin Begemann, Phil Lee, Richard Anney, Mark A. Bellgrove, Lisa Jones, Andreas J. Forstner, Agnieszka Słopień, Hilary Coon, Dong Li, Alessandro Serretti, Carsten Horn, Christos Pantelis, Ryan L. Collins, David M. Howard, Lucía Colodro-Conde, Pippa A. Thomson, Martin Hautzinger, Alysa E. Doyle, Julie Hagstrøm, Oliver S. P. Davis, Karen S. Mitchell, Jordan W. Smoller, Michael Strober, John I. Nurnberger, Andrea G. Ludolph, Monika Budde, Anna Maaser, Lambertus Klei, Aribert Rothenberger, Yulia Worbe, Fabian Streit, James L. Kennedy, Barbara E. Stranger, Ashley Dumont, Jianxin Shi, Dale R. Nyholt, Craig Johnson, Jonna Kuntsi, Yun-Joo Koh, Loes M. Olde Loohuis, Robert B. Freedman, Anke Hinney, Susanne Walitza, Enrico Domenici, Margarita Rivera, Sodahm Kook, Erica Greenberg, Tetyana Zayats, Josef Frank, Gary A. Heiman, Andrew McQuillin, Abraham Reichenberg, Piotr M. Czerski, Humberto Nicolini, Lee P.H., Anttila V., Won H., Feng Y.-C.A., Rosenthal J., Zhu Z., Tucker-Drob E.M., Nivard M.G., Grotzinger A.D., Posthuma D., Wang M.M.-J., Yu D., Stahl E.A., Walters R.K., Anney R.J.L., Duncan L.E., Ge T., Adolfsson R., Banaschewski T., Belangero S., Cook E.H., Coppola G., Derks E.M., Hoekstra P.J., Kaprio J., Keski-Rahkonen A., Kirov G., Kranzler H.R., Luykx J.J., Rohde L.A., Zai C.C., Agerbo E., Arranz M.J., Asherson P., Baekvad-Hansen M., Baldursson G., Bellgrove M., Belliveau R.A., Buitelaar J., Burton C.L., Bybjerg-Grauholm J., Casas M., Cerrato F., Chambert K., Churchhouse C., Cormand B., Crosbie J., Dalsgaard S., Demontis D., Doyle A.E., Dumont A., Elia J., Grove J., Gudmundsson O.O., Haavik J., Hakonarson H., Hansen C.S., Hartman C.A., Hawi Z., Hervas A., Hougaard D.M., Howrigan D.P., Huang H., Kuntsi J., Langley K., Lesch K.-P., Leung P.W.L., Loo S.K., Martin J., Martin A.R., McGough J.J., Medland S.E., Moran J.L., Mors O., Mortensen P.B., Oades R.D., Palmer D.S., Pedersen C.B., Pedersen M.G., Peters T., Poterba T., Poulsen J.B., Ramos-Quiroga J.A., Reif A., Ribases M., Rothenberger A., Rovira P., Sanchez-Mora C., Satterstrom F.K., Schachar R., Artigas M.S., Steinberg S., Stefansson H., Turley P., Walters G.B., Werge T., Zayats T., Arking D.E., Bettella F., Buxbaum J.D., Christensen J.H., Collins R.L., Coon H., De Rubeis S., Delorme R., Grice D.E., Hansen T.F., Holmans P.A., Hope S., Hultman C.M., Klei L., Ladd-Acosta C., Magnusson P., Naerland T., Nyegaard M., Pinto D., Qvist P., Rehnstrom K., Reichenberg A., Reichert J., Roeder K., Rouleau G.A., Saemundsen E., Sanders S.J., Sandin S., St Pourcain B., Stefansson K., Sutcliffe J.S., Talkowski M.E., Weiss L.A., Willsey A.J., Agartz I., Akil H., Albani D., Alda M., Als T.D., Anjorin A., Backlund L., Bass N., Bauer M., Baune B.T., Bellivier F., Bergen S.E., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boen E., Budde M., Bunney W., Burmeister M., Byerley W., Byrne E.M., Cichon S., Clarke T.-K., Coleman J.R.I., Craddock N., Curtis D., Czerski P.M., Dale A.M., Dalkner N., Dannlowski U., Degenhardt F., Di Florio A., Elvsashagen T., Etain B., Fischer S.B., Forstner A.J., Forty L., Frank J., Frye M., Fullerton J.M., Gade K., Gaspar H.A., Gershon E.S., Gill M., Goes F.S., Gordon S.D., Gordon-Smith K., Green M.J., Greenwood T.A., Grigoroiu-Serbanescu M., Guzman-Parra J., Hauser J., Hautzinger M., Heilbronner U., Herms S., Hoffmann P., Holland D., Jamain S., Jones I., Jones L.A., Kandaswamy R., Kelsoe J.R., Kennedy J.L., Joachim O.K., Kittel-Schneider S., Kogevinas M., Koller A.C., Lavebratt C., Lewis C.M., Li Q.S., Lissowska J., Loohuis L.M.O., Lucae S., Maaser A., Malt U.F., Martin N.G., Martinsson L., McElroy S.L., McMahon F.J., McQuillin A., Melle I., Metspalu A., Millischer V., Mitchell P.B., Montgomery G.W., Morken G., Morris D.W., Muller-Myhsok B., Mullins N., Myers R.M., Nievergelt C.M., Nordentoft M., Adolfsson A.N., Nothen M.M., Ophoff R.A., Owen M.J., Paciga S.A., Pato C.N., Pato M.T., Perlis R.H., Perry A., Potash J.B., Reinbold C.S., Rietschel M., Rivera M., Roberson M., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Sigurdsson E., Smeland O.B., Stordal E., Streit F., Strohmaier J., Thorgeirsson T.E., Treutlein J., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Wang Y., Witt S.H., Zandi P., Adan R.A.H., Alfredsson L., Ando T., Aschauer H., Baker J.H., Bencko V., Bergen A.W., Birgegard A., Perica V.B., Brandt H., Burghardt R., Carlberg L., Cassina M., Clementi M., Courtet P., Crawford S., Crow S., Crowley J.J., Danner U.N., Davis O.S.P., Degortes D., DeSocio J.E., Dick D.M., Dina C., Docampo E., Egberts K., Ehrlich S., Espeseth T., Fernandez-Aranda F., Fichter M.M., Foretova L., Forzan M., Gambaro G., Giegling I., Gonidakis F., Gorwood P., Mayora M.G., Guo Y., Halmi K.A., Hatzikotoulas K., Hebebrand J., Helder S.G., Herpertz-Dahlmann B., Herzog W., Hinney A., Imgart H., Jimenez-Murcia S., Johnson C., Jordan J., Julia A., Kaminska D., Karhunen L., Karwautz A., Kas M.J.H., Kaye W.H., Kennedy M.A., Kim Y.-R., Klareskog L., Klump K.L., Knudsen G.P.S., Landen M., Le Hellard S., Levitan R.D., Li D., Lichtenstein P., Maj M., Marsal S., McDevitt S., Mitchell J., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., O'Toole J.K., Padyukov L., Pantel J., Papezova H., Rabionet R., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Roberts M., Rujescu D., Rybakowski F., Scherag A., Schmidt U., Seitz J., Slachtova L., Slof-Op't Landt M.C.T., Slopien A., Sorbi S., Southam L., Strober M., Tortorella A., Tozzi F., Treasure J., Tziouvas K., van Elburg A.A., Wade T.D., Wagner G., Walton E., Watson H.J., Wichmann H.-E., Woodside D.B., Zeggini E., Zerwas S., Zipfel S., Adams M.J., Andlauer T.F.M., Berger K., Binder E.B., Boomsma D.I., Castelao E., Colodro-Conde L., Direk N., Docherty A.R., Domenici E., Domschke K., Dunn E.C., Foo J.C., de. Geus E.J.C., Grabe H.J., Hamilton S.P., Horn C., Hottenga J.-J., Howard D., Ising M., Kloiber S., Levinson D.F., Lewis G., Magnusson P.K.E., Mbarek H., Middeldorp C.M., Mostafavi S., Nyholt D.R., Penninx B.W., Peterson R.E., Pistis G., Porteous D.J., Preisig M., Quiroz J.A., Schaefer C., Schulte E.C., Shi J., Smith D.J., Thomson P.A., Tiemeier H., Uher R., van der Auwera S., Weissman M.M., Alexander M., Begemann M., Bramon E., Buccola N.G., Cairns M.J., Campion D., Carr V.J., Cloninger C.R., Cohen D., Collier D.A., Corvin A., DeLisi L.E., Donohoe G., Dudbridge F., Duan J., Freedman R., Gejman P.V., Golimbet V., Godard S., Ehrenreich H., Hartmann A.M., Henskens F.A., Ikeda M., Iwata N., Jablensky A.V., Joa I., Jonsson E.G., Kelly B.J., Knight J., Konte B., Laurent-Levinson C., Lee J., Lencz T., Lerer B., Loughland C.M., Malhotra A.K., Mallet J., McDonald C., Mitjans M., Mowry B.J., Murphy K.C., Murray R.M., O'Neill F.A., Oh S.-Y., Palotie A., Pantelis C., Pulver A.E., Petryshen T.L., Quested D.J., Riley B., Sanders A.R., Schall U., Schwab S.G., Scott R.J., Sham P.C., Silverman J.M., Sim K., Steixner A.A., Tooney P.A., van Os J., Vawter M.P., Walsh D., Weiser M., Wildenauer D.B., Williams N.M., Wormley B.K., Zhang F., Androutsos C., Arnold P.D., Barr C.L., Barta C., Bey K., Bienvenu O.J., Black D.W., Brown L.W., Budman C., Cath D., Cheon K.-A., Ciullo V., Coffey B.J., Cusi D., Davis L.K., Denys D., Depienne C., Dietrich A., Eapen V., Falkai P., Fernandez T.V., Garcia-Delgar B., Geller D.A., Gilbert D.L., Grados M.A., Greenberg E., Grunblatt E., Hagstrom J., Hanna G.L., Hartmann A., Hedderly T., Heiman G.A., Heyman I., Hong H.J., Huang A., Huyser C., Ibanez-Gomez L., Khramtsova E.A., Kim Y.K., Kim Y.-S., King R.A., Koh Y.-J., Konstantinidis A., Kook S., Kuperman S., Leventhal B.L., Lochner C., Ludolph A.G., Madruga-Garrido M., Malaty I., Maras A., McCracken J.T., Meijer I.A., Mir P., Morer A., Muller-Vahl K.R., Munchau A., Murphy T.L., Naarden A., Nagy P., Nestadt G., Nestadt P.S., Nicolini H., Nurmi E.L., Okun M.S., Paschou P., Piras F., Pittenger C., Plessen K.J., Richter M.A., Rizzo R., Robertson M., Roessner V., Ruhrmann S., Samuels J.F., Sandor P., Schlogelhofer M., Shin E.-Y., Singer H., Song D.-H., Song J., Spalletta G., Stein D.J., Stewart S.E., Storch E.A., Stranger B., Stuhrmann M., Tarnok Z., Tischfield J.A., Tubing J., Visscher F., Vulink N., Wagner M., Walitza S., Wanderer S., Woods M., Worbe Y., Zai G., Zinner S.H., Sullivan P.F., Franke B., Daly M.J., Bulik C.M., McIntosh A.M., O'Donovan M.C., Zheutlin A., Andreassen O.A., Borglum A.D., Breen G., Edenberg H.J., Fanous A.H., Faraone S.V., Gelernter J., Mathews C.A., Mattheisen M., Mitchell K.S., Neale M.C., Nurnberger J.I., Ripke S., Santangelo S.L., Scharf J.M., Stein M.B., Thornton L.M., Walters J.T.R., Wray N.R., Geschwind D.H., Neale B.M., Kendler K.S., Smoller J.W., Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, APH - Digital Health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Kas lab, Adult Psychiatry, Child Psychiatry, ANS - Complex Trait Genetics, Aarno Palotie / Principal Investigator, Jaakko Kaprio / Principal Investigator, Centre of Excellence in Complex Disease Genetics, Genetic Epidemiology, Department of Public Health, University Management, Anna Keski-Rahkonen / Principal Investigator, Department of Medical and Clinical Genetics, Clinicum, HUS Psychiatry, Institute for Molecular Medicine Finland, Research Programs Unit, Genomics of Neurological and Neuropsychiatric Disorders, Biological Psychology, Complex Trait Genetics, APH - Methodology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Lee, P. H., Anttila, V., Won, H., Feng, Y. -C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Posthuma, D., Wang, M. M. -J., Yu, D., Stahl, E. A., Walters, R. K., Anney, R. J. L., Duncan, L. E., Ge, T., Adolfsson, R., Banaschewski, T., Belangero, S., Cook, E. H., Coppola, G., Derks, E. M., Hoekstra, P. J., Kaprio, J., Keski-Rahkonen, A., Kirov, G., Kranzler, H. R., Luykx, J. J., Rohde, L. A., Zai, C. C., Agerbo, E., Arranz, M. J., Asherson, P., Baekvad-Hansen, M., Baldursson, G., Bellgrove, M., Belliveau, R. A., Buitelaar, J., Burton, C. L., Bybjerg-Grauholm, J., Casas, M., Cerrato, F., Chambert, K., Churchhouse, C., Cormand, B., Crosbie, J., Dalsgaard, S., Demontis, D., Doyle, A. E., Dumont, A., Elia, J., Grove, J., Gudmundsson, O. O., Haavik, J., Hakonarson, H., Hansen, C. S., Hartman, C. A., Hawi, Z., Hervas, A., Hougaard, D. M., Howrigan, D. P., Huang, H., Kuntsi, J., Langley, K., Lesch, K. -P., Leung, P. W. L., Loo, S. K., Martin, J., Martin, A. R., Mcgough, J. J., Medland, S. E., Moran, J. L., Mors, O., Mortensen, P. B., Oades, R. D., Palmer, D. S., Pedersen, C. B., Pedersen, M. G., Peters, T., Poterba, T., Poulsen, J. B., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Rothenberger, A., Rovira, P., Sanchez-Mora, C., Satterstrom, F. K., Schachar, R., Artigas, M. S., Steinberg, S., Stefansson, H., Turley, P., Walters, G. B., Werge, T., Zayats, T., Arking, D. E., Bettella, F., Buxbaum, J. D., Christensen, J. H., Collins, R. L., Coon, H., De Rubeis, S., Delorme, R., Grice, D. E., Hansen, T. F., Holmans, P. A., Hope, S., Hultman, C. M., Klei, L., Ladd-Acosta, C., Magnusson, P., Naerland, T., Nyegaard, M., Pinto, D., Qvist, P., Rehnstrom, K., Reichenberg, A., Reichert, J., Roeder, K., Rouleau, G. A., Saemundsen, E., Sanders, S. J., Sandin, S., St Pourcain, B., Stefansson, K., Sutcliffe, J. S., Talkowski, M. E., Weiss, L. A., Willsey, A. J., Agartz, I., Akil, H., Albani, D., Alda, M., Als, T. D., Anjorin, A., Backlund, L., Bass, N., Bauer, M., Baune, B. T., Bellivier, F., Bergen, S. E., Berrettini, W. H., Biernacka, J. M., Blackwood, D. H. R., Boen, E., Budde, M., Bunney, W., Burmeister, M., Byerley, W., Byrne, E. M., Cichon, S., Clarke, T. -K., Coleman, J. R. I., Craddock, N., Curtis, D., Czerski, P. M., Dale, A. M., Dalkner, N., Dannlowski, U., Degenhardt, F., Di Florio, A., Elvsashagen, T., Etain, B., Fischer, S. B., Forstner, A. J., Forty, L., Frank, J., Frye, M., Fullerton, J. M., Gade, K., Gaspar, H. A., Gershon, E. S., Gill, M., Goes, F. S., Gordon, S. D., Gordon-Smith, K., Green, M. J., Greenwood, T. A., Grigoroiu-Serbanescu, M., Guzman-Parra, J., Hauser, J., Hautzinger, M., Heilbronner, U., Herms, S., Hoffmann, P., Holland, D., Jamain, S., Jones, I., Jones, L. A., Kandaswamy, R., Kelsoe, J. R., Kennedy, J. L., Joachim, O. K., Kittel-Schneider, S., Kogevinas, M., Koller, A. C., Lavebratt, C., Lewis, C. M., Li, Q. S., Lissowska, J., Loohuis, L. M. O., Lucae, S., Maaser, A., Malt, U. F., Martin, N. G., Martinsson, L., Mcelroy, S. L., Mcmahon, F. J., Mcquillin, A., Melle, I., Metspalu, A., Millischer, V., Mitchell, P. B., Montgomery, G. W., Morken, G., Morris, D. W., Muller-Myhsok, B., Mullins, N., Myers, R. M., Nievergelt, C. M., Nordentoft, M., Adolfsson, A. N., Nothen, M. M., Ophoff, R. A., Owen, M. J., Paciga, S. A., Pato, C. N., Pato, M. T., Perlis, R. H., Perry, A., Potash, J. B., Reinbold, C. S., Rietschel, M., Rivera, M., Roberson, M., Schalling, M., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Sigurdsson, E., Smeland, O. B., Stordal, E., Streit, F., Strohmaier, J., Thorgeirsson, T. E., Treutlein, J., Turecki, G., Vaaler, A. E., Vieta, E., Vincent, J. B., Wang, Y., Witt, S. H., Zandi, P., Adan, R. A. H., Alfredsson, L., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Bergen, A. W., Birgegard, A., Perica, V. B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
Subjects: Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Published: 2019
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23. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Author: A. Jeremy Willsey, Thomas V. Fernandez, Dongmei Yu, Robert A. King, Andrea Dietrich, Jinchuan Xing, Stephan J. Sanders, Jeffrey D. Mandell, Alden Y. Huang, Petra Richer, Louw Smith, Shan Dong, Kaitlin E. Samocha, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jay A. Tischfield, Jeremiah M. Scharf, Matthew W. State, Gary A. Heiman, Mohamed Abdulkadir, Julia Bohnenpoll, Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Lonneke Elzerman, Odette Fründt, Blanca Garcia-Delgar, Erika Gedvilaite, Donald L. Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Pieter J. Hoekstra, Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Andreas Lamerz, Bennett Leventhal, Andrea G. Ludolph, Claudia Lühr da Silva, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Alexander Münchau, Tara L. Murphy, Cara Nasello, Thaïra J.C. Openneer, Kerstin J. Plessen, Veit Roessner, Stephan Sanders, Eun-Young Shin, Deborah A. Sival, Dong-Ho Song, Jungeun Song, Anne Marie Stolte, Nawei Sun, Jennifer Tübing, Frank Visscher, Michael F. Walker, Sina Wanderer, Shuoguo Wang, Martin Woods, Yeting Zhang, Anbo Zhou, Samuel H. Zinner, Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Cornelia Illmann, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. MaMahon, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Reproduction & Development (AR&D), Human genetics, Other departments, and Child Psychiatry
Subjects: 0301 basic medicine, Proband, Adult, Male, Parents, INTELLECTUAL DISABILITY, FUNCTIONAL GENOMICS EXPERIMENTS, DNA-SEQUENCING DATA, AUTISM SPECTRUM DISORDERS, Cell Cycle Proteins, Receptors, Cell Surface, Biology, medicine.disease_cause, Bioinformatics, Tourette syndrome, Article, TIC DISORDERS, Cohort Studies, 03 medical and health sciences, medicine, Odds Ratio, Missense mutation, Humans, Genetic Predisposition to Disease, Copy-number variation, Child, Gene, Exome sequencing, Genetics, COPY NUMBER VARIANTS, Mutation, MUTATIONS, General Neuroscience, PSYCHIATRIC-DISORDERS, Intracellular Signaling Peptides and Proteins, Genetic Variation, Proteins, NIPBL, OBSESSIVE-COMPULSIVE DISORDER, LANGE-SYNDROME, Sequence Analysis, DNA, medicine.disease, Cadherins, Phosphoproteins, Fibronectins, 030104 developmental biology, Female, Tourette Syndrome
Abstract: Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. Video Abstract [Figure presented]
Published: 2017
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24. Vanishing White Matter Disease in a Spanish Population

Author: Naiara Olabarrieta-Hoyos, Veronica Gonzalez-Alvarez, Mar O'Callaghan, Victoria Cusi, Rebeca Losada-Del Pozo, Eulàlia Turón-Viñas, David Conejo Moreno, Javier Aguirre-Rodríguez, Judith Armstrong-Moron, Concha Sierra-Córcoles, Mercè Pineda, Luis González Gutiérrez-Solana, Eduardo López-Laso, Marcos Madruga-Garrido, and Jordi Muchart
Subjects: leukodystrophy, Pediatrics, medicine.medical_specialty, Ataxia, Bioinformatics, lcsh:RC346-429, White matter, Leukoencephalopathy, Epilepsy, Atrophy, children, medicine, genetics, Spasticity, lcsh:Neurology. Diseases of the nervous system, vanishing white matter disease, business.industry, Leukodystrophy, medicine.disease, Short Review, Hemiparesis, medicine.anatomical_structure, Spain, pathology, medicine.symptom, business
Abstract: Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor ( eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5.
Published: 2014

25. Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families

Author: Paul Sandor, Pablo Mir, Urszula Szymańska, Sandra Dehning, Anastasia Koumoula, Gerd Lehmkuhl, Marcos Madruga-Garrido, Markus M. Nöthen, Renata Rizzo, Norbert Müller, Peter Zill, Iordanis Karagiannidis, Christos Androutsos, Luca Farkas, Vaia Tsironi, Peter Nagy, Zachos Anastasiou, Johannes Hebebrand, Csaba Barta, Peristera Paschou, Vasileios Stathias, Cathy L. Barr, Tomasz Wolańczyk, and Zsanett Tarnok
Subjects: Genetics, medicine.medical_specialty, Haplotype, Nonsense mutation, Histaminergic, Medizin, Single-nucleotide polymorphism, Biology, Histidine Decarboxylase, medicine.disease, Tourette syndrome, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Cohort Studies, Neurodevelopmental disorder, Haplotypes, Molecular genetics, medicine, Humans, Allele, Genetics (clinical), Genetic Association Studies, Tourette Syndrome
Abstract: Background Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.
Published: 2013

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25 results on '"Marcos, Madruga"'

1. Validation of a Set of Instruments to Assess Patient- and Caregiver-Oriented Measurements in Spinal Muscular Atrophy: Results of the SMA-TOOL Study

2. Pain in Children and Adolescents with Spinal Muscular Atrophy: A Longitudinal Study from a Patient Registry

3. Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency

4. Synaptic processes and immune-related pathways implicated in Tourette syndrome

5. Desmin Modulates Muscle Cell Adhesion and Migration

6. NOVEL intronic CAPN3 Roma mutation alters splicing causing RNA mediated decay

7. Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study

8. Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

9. Investigation of gene-environment interactions in relation to tic severity

10. Vanishing White Matter Disease in a Spanish Population

11. Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

12. Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group

13. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

14. Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders

15. Clinical precursors of tics: an EMTICS study

16. Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder

17. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy

18. European Multicentre Tics in Children Studies (EMTICS)

19. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

20. Investigation of previously implicated genetic variants in chronic tic disorders

21. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy

22. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

23. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

24. Vanishing White Matter Disease in a Spanish Population

25. Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families

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25 results on '"Marcos, Madruga"'

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