Search

Your search keyword '"Vermeesch, J."' showing total 366 results
Start Over Author "Vermeesch, J."
366 results on '"Vermeesch, J."'

2. A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium

Author

Gur, RE, Bassett, AS, McDonald-McGinn, DM, Bearden, CE, Chow, E, Emanuel, BS, Owen, M, Swillen, A, Van den Bree, M, Vermeesch, J, Vorstman, JAS, Warren, S, Lehner, T, and Morrow, B

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Genetics, Human Genome, Schizophrenia, Neurosciences, Biotechnology, Serious Mental Illness, Brain Disorders, Mental Health, Pediatric, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Aged, Child, Cohort Studies, Cooperative Behavior, DNA Copy Number Variations, Data Mining, DiGeorge Syndrome, Female, Genetic Predisposition to Disease, Genome, Humans, Male, Middle Aged, Models, Genetic, Models, Neurological, Phenotype, Scholarly Communication, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis. The genomic approach includes a combination of whole-genome sequencing and genome-wide microarray technologies, allowing the investigation of all possible DNA variation and gene pathways influencing the schizophrenia-relevant phenotypic expression. A phenotypically rich data set provides a psychiatrically well-characterized sample of unprecedented size (n=1616) that informs the neurobehavioral developmental course of 22q11DS. This combined set of phenotypic and genomic data will enable hypothesis testing to elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum disorders.

Published
2017

4. Position statement from the International Society for Prenatal Diagnosis on the use of non-invasive prenatal testing for the detection of fetal chromosomal conditions in singleton pregnancies

Author

Hui, L, Ellis, K, Mayen, D, Pertile, MDD, Reimers, R, Sun, L, Vermeesch, J, Vora, NLL, Chitty, LSS, SPD, BOD, Hui, L, Ellis, K, Mayen, D, Pertile, MDD, Reimers, R, Sun, L, Vermeesch, J, Vora, NLL, Chitty, LSS, and SPD, BOD

Abstract

Key points What is already known about this topic? In 2015, the International Society for Prenatal Diagnosis (ISPD) published its first position statement on the use of non‐invasive prenatal testing (NIPT) to screen for aneuploidy. Widespread uptake across the globe and subsequent published research has shed new light on test performance and implementation issues. What does this study add? This new position statement replaces the 2015 statement with updated information on the current technologies, clinical experience, and implementation practices. As an international organization, ISPD recognizes that there are important population‐specific considerations in the organization of prenatal screening and diagnosis. These opinions are designed to apply to high income settings where prenatal screening for aneuploidy is an established part of antenatal care. This position statement is not a clinical practice guideline but represents the consensus opinion of the current ISPD Board based on the current state of knowledge and clinical practice.

Published
2023

5. Recent developments in genetics and medically assisted reproduction: from research to clinical applications

Author

Harper, J. C., Aittomäki, K., Borry, P., Cornel, M. C., de Wert, G., Dondorp, W., Geraedts, J., Gianaroli, L., Ketterson, K., Liebaers, I., Lundin, K., Mertes, H., Morris, M., Pennings, G., Sermon, K., Spits, C., Soini, S., van Montfoort, A. P. A., Veiga, A., Vermeesch, J. R., Viville, S., Macek Jr., M., and on behalf of the European Society of Human Reproduction and Embryology and European Society of Human Genetics

Published
2018
Full Text
View/download PDF

10. O-236 A multi-omics genome-plus-transcriptome single-cell atlas of human pre-implantation development reveals the impact of chromosome instability on cell function within the embryo

Author

Fernandez, E, primary, Sifrim, A, additional, Chappell, J, additional, Demeulemeester, J, additional, Van der Haegen, M, additional, Brown, D, additional, Theunis, K, additional, Van Herck, J, additional, Vandereyken, K, additional, Ponting, C, additional, Vermeesch, J, additional, Peeraer, K, additional, Debrock, S, additional, Pasque, V, additional, and Voet, T, additional

Published
2022
Full Text
View/download PDF

12. O-042 ESHRE good practice recommendations on chromosomal mosaicism

Author

De Rycke, M, primary, Capalbo, A, additional, Coonen, E, additional, Coticchio, G, additional, Fiorentino, F, additional, Goossens, V, additional, MCheik, S, additional, Rubio, C, additional, Sermon, K, additional, Sfontouris, I, additional, Spits, C, additional, Vermeesch, J, additional, Vermeulen, N, additional, Wells, D, additional, Zambelli, F, additional, and Kakourou, G, additional

Published
2022
Full Text
View/download PDF

13. A normative chart for cognitive development in a genetically selected population

Author

Fiksinski, A.M., Bearden, C.E., Bassett, A.S., Kahn, R.S., Zinkstok, J.R., Hooper, S.R., Tempelaar, W., McDonald-McGinn, D., Swillen, A., Emanuel, B., Morrow, B., Gur, R., Chow, E., Bree, M. van, Vermeesch, J., Warren, S., Owen, M., Amelsvoort, T. van, Eliez, S., Gothelf, D., Arango, C., Kates, W., Simon, T., Murphy, K., Repetto, G., Suner, D.H., Vicari, S., Cubells, J., Armando, M., Philip, N., Campbell, L., Garcia-Minaur, S., Schneider, M., Shashi, V., Vorstman, J., Breetvelt, E.J., Fiksinski, A.M., Bearden, C.E., Bassett, A.S., Kahn, R.S., Zinkstok, J.R., Hooper, S.R., Tempelaar, W., McDonald-McGinn, D., Swillen, A., Emanuel, B., Morrow, B., Gur, R., Chow, E., Bree, M. van, Vermeesch, J., Warren, S., Owen, M., Amelsvoort, T. van, Eliez, S., Gothelf, D., Arango, C., Kates, W., Simon, T., Murphy, K., Repetto, G., Suner, D.H., Vicari, S., Cubells, J., Armando, M., Philip, N., Campbell, L., Garcia-Minaur, S., Schneider, M., Shashi, V., Vorstman, J., and Breetvelt, E.J.

Abstract

Item does not contain fulltext, Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.

Published
2022

17. 60 Comprehensive genome-wide analysis of non-invasive test data allows accurate cancer prediction: a retrospective analysis of over 85.000 pregnancies

Author

Lenaerts, L, primary, Brison, N, additional, Maggen, C, additional, Vancoillie, L, additional, Che, H, additional, Vandenberghe, P, additional, Dierickx, D, additional, Michaux, L, additional, Dewaele, B, additional, Neven, P, additional, Floris, G, additional, Jatsenko, T, additional, Van Calsteren, K, additional, Vandecaveye, V, additional, Dehaspe, L, additional, Devriendt, K, additional, Legius, E, additional, Van Den Bogaert, K, additional, Vermeesch, J, additional, and Amant, F, additional

Published
2021
Full Text
View/download PDF

20. Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome

Author

Davies, R. W., Fiksinski, A. M., Breetvelt, E. J., Williams, N. M., Hooper, S. R., Monfeuga, T., Bassett, A. S., Owen, M. J., Gur, R. E., Morrow, B. E., McDonald-McGinn, D. M., Swillen, A., Chow, E. W. C., van den Bree, M., Emanuel, B. S., Vermeesch, J. R., van Amelsvoort, T., Arango, C., Armando, M., Campbell, L. E., Cubells, J. F., Eliez, S., Garcia-Minaur, S., Gothelf, D., Kates, W. R., Murphy, K. C., Murphy, C. M., Murphy, D. G., Philip, N., Repetto, G. M., Shashi, V., Simon, T. J., Suner, D. H., Vicari, Stefano, Scherer, S. W., Epstein, M. P., Warren, S. T., Morrison, S., Chawner, S., Vingerhoets, C., Breckpot, J., Vergaelen, E., Vogels, A., Monks, S., Prasad, S. E., Sandini, C., Schneider, M., Maeder, J., Fraguas, D., Evers, R., Tassone, F., Morey-Canyelles, J., Ousley, O. Y., Antshel, K. M., Fremont, W., Fritsch, R., Ornstein, C., Daly, E. M., Costain, G. A., Boot, E., Heung, T., Crowley, T. B., Zackai, E. H., Calkins, M. E., Gur, R. C., Mccabe, K. L., Busa, T., Schoch, K., Pontillo, M., Duijff, S. N., Kahn, R. S., Houben, Mariasofia, Kushan, L., Jalbrzikowski, M., Carmel, M., Mekori-Domachevsky, E., Michaelovsky, E., Weinberger, R., Bearden, C. E., Vorstman, J. A. S., Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, [SDV]Life Sciences [q-bio], INTELLIGENCE, Medical and Health Sciences, Cohort Studies, ddc:616.89, 0302 clinical medicine, Borderline intellectual functioning, Risk Factors, Intellectual disability, 2.1 Biological and endogenous factors, PREMORBID IQ, Cognitive decline, Aetiology, Child, ComputingMilieux_MISCELLANEOUS, Intelligence quotient, ABNORMALITIES, General Medicine, Middle Aged, Serious Mental Illness, Mental Health, Phenotype, Schizophrenia, 030220 oncology & carcinogenesis, Child, Preschool, Cohort, Female, Clinical psychology, Adult, Psychosis, Adolescent, Immunology, behavioral disciplines and activities, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Young Adult, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, PSYCHOSIS, Clinical Research, Intellectual Disability, Genetic variation, Behavioral and Social Science, mental disorders, medicine, Genetics, DiGeorge Syndrome, Humans, Cognitive Dysfunction, Preschool, METAANALYSIS, International 22q11.2 Brain and Behavior Consortium, Aged, DECLINE, reliability, business.industry, Prevention, cognitive-development, Genetic Variation, PERFORMANCE, medicine.disease, Brain Disorders, schizophrenia, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, business
Abstract

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.Polygenic risk scores are nearing a level of differentiation required for their clinical utility in risk prediction in populations with high-risk rare pathogenic genetic variants.

Published
2020
Full Text
View/download PDF

26. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome

Author

van Bon, B W M, Mefford, H C, Menten, B, Koolen, D A, Sharp, A J, Nillesen, W M, Innis, J W, de Ravel, T J L, Mercer, C L, Fichera, M, Stewart, H, Connell, L E, Õunap, K, Lachlan, K, Castle, B, Van der Aa, N, van Ravenswaaij, C, Nobrega, M A, Serra-Juhé, C, Simonic, I, de Leeuw, N, Pfundt, R, Bongers, E M, Baker, C, Finnemore, P, Huang, S, Maloney, V K, Crolla, J A, van Kalmthout, M, Elia, M, Vandeweyer, G, Fryns, J P, Janssens, S, Foulds, N, Reitano, S, Smith, K, Parkel, S, Loeys, B, Woods, C G, Oostra, A, Speleman, F, Pereira, A C, Kurg, A, Willatt, L, Knight, S J L, Vermeesch, J R, Romano, C, Barber, J C, Mortier, G, Pérez-Jurado, L A, Kooy, F, Brunner, H G, Eichler, E E, Kleefstra, T, and de Vries, B B A

Published
2009
Full Text
View/download PDF

32. Cryptic deletions are a common finding in “balanced” reciprocal and complex chromosome rearrangements: a study of 59 patients

Author

De Gregori, M, Ciccone, R, Magini, P, Pramparo, T, Gimelli, S, Messa, J, Novara, F, Vetro, A, Rossi, E, Maraschio, P, Bonaglia, M C, Anichini, C, Ferrero, G B, Silengo, M, Fazzi, E, Zatterale, A, Fischetto, R, Previderé, C, Belli, S, Turci, A, Calabrese, G, Bernardi, F, Meneghelli, E, Riegel, M, Rocchi, M, Guerneri, S, Lalatta, F, Zelante, L, Romano, C, Fichera, Ma, Mattina, T, Arrigo, G, Zollino, M, Giglio, S, Lonardo, F, Bonfante, A, Ferlini, A, Cifuentes, F, Van Esch, H, Backx, L, Schinzel, A, Vermeesch, J R, and Zuffardi, O

Published
2007

35. Missense variants in TAF1 and developmental phenotypes: Challenges of determining pathogenicity

Author

Cheng, H, Capponi, S, Wakeling, E, Marchi, E, Li, Q, Zhao, M, Weng, C, Stefan, PG, Ahlfors, H, Kleyner, R, Rope, A, Lumaka, A, Lukusa, P, Devriendt, K, Vermeesch, J, Posey, JE, Palmer, EE, Murray, L, Leon, E, Diaz, J, Worgan, L, Mallawaarachchi, A, Vogt, J, de Munnik, SA, Dreyer, L, Baynam, G, Ewans, L, Stark, Z, Lunke, S, Gonçalves, AR, Soares, G, Oliveira, J, Fassi, E, Willing, M, Waugh, JL, Faivre, L, Riviere, JB, Moutton, S, Mohammed, S, Payne, K, Walsh, L, Begtrup, A, Guillen Sacoto, MJ, Douglas, G, Alexander, N, Buckley, MF, Mark, PR, Adès, LC, Sandaradura, SA, Lupski, JR, Roscioli, T, Agrawal, PB, Kline, AD, Wang, K, Timmers, HTM, Lyon, GJ, Cheng, H, Capponi, S, Wakeling, E, Marchi, E, Li, Q, Zhao, M, Weng, C, Stefan, PG, Ahlfors, H, Kleyner, R, Rope, A, Lumaka, A, Lukusa, P, Devriendt, K, Vermeesch, J, Posey, JE, Palmer, EE, Murray, L, Leon, E, Diaz, J, Worgan, L, Mallawaarachchi, A, Vogt, J, de Munnik, SA, Dreyer, L, Baynam, G, Ewans, L, Stark, Z, Lunke, S, Gonçalves, AR, Soares, G, Oliveira, J, Fassi, E, Willing, M, Waugh, JL, Faivre, L, Riviere, JB, Moutton, S, Mohammed, S, Payne, K, Walsh, L, Begtrup, A, Guillen Sacoto, MJ, Douglas, G, Alexander, N, Buckley, MF, Mark, PR, Adès, LC, Sandaradura, SA, Lupski, JR, Roscioli, T, Agrawal, PB, Kline, AD, Wang, K, Timmers, HTM, and Lyon, GJ

Abstract

We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability [ID] syndrome) (MIM# 300966) caused by pathogenic variants involving the X-linked gene TATA-box binding protein associated factor 1 (TAF1), which participates in RNA polymerase II transcription. The initial study reported 11 families, and the syndrome was defined as presenting early in life with hypotonia, facial dysmorphia, and developmental delay that evolved into ID and/or autism spectrum disorder. We have now identified an additional 27 families through a genotype-first approach. Familial segregation analysis, clinical phenotyping, and bioinformatics were capitalized on to assess potential variant pathogenicity, and molecular modeling was performed for those variants falling within structurally characterized domains of TAF1. A novel phenotypic clustering approach was also applied, in which the phenotypes of affected individuals were classified using 51 standardized Human Phenotype Ontology terms. Phenotypes associated with TAF1 variants show considerable pleiotropy and clinical variability, but prominent among previously unreported effects were brain morphological abnormalities, seizures, hearing loss, and heart malformations. Our allelic series broadens the phenotypic spectrum of the TAF1/MRXS33 ID syndrome and the range of TAF1 molecular defects in humans. It also illustrates the challenges for determining the pathogenicity of inherited missense variants, particularly for a gene mapping to chromosome X.

Published
2020

36. Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Author

Cleynen, I., Engchuan, W., Hestand, M. S., Heung, T., Holleman, A. M., Johnston, H. R., Monfeuga, T., McDonald-McGinn, D. M., Gur, R. E., Morrow, B. E., Swillen, A., Vorstman, J. A. S., Bearden, C. E., Chow, E. W. C., van den Bree, M., Emanuel, B. S., Vermeesch, J. R., Warren, S. T., Owen, M. J., Chopra, P., Cutler, D. J., Duncan, R., Kotlar, A. V., Mulle, J. G., Voss, A. J., Zwick, M. E., Diacou, A., Golden, A., Guo, T., Lin, J. -R., Wang, T., Zhang, Z., Zhao, Yu Yang, Marshall, C., Merico, D., Jin, A., Lilley, B., Salmons, H. I., Tran, O., Holmans, P., Pardinas, A., Walters, J. T. R., Demaerel, W., Boot, E., Butcher, N. J., Costain, G. A., Lowther, C., Evers, R., van Amelsvoort, T. A. M. J., van Duin, E., Vingerhoets, C., Breckpot, J., Devriendt, K., Vergaelen, E., Vogels, A., Crowley, T. B., Mcginn, D. E., Moss, E. M., Sharkus, R. J., Unolt, M., Zackai, E. H., Calkins, M. E., Gallagher, R. S., Gur, R. C., Tang, S. X., Fritsch, R., Ornstein, C., Repetto, G. M., Breetvelt, E., Duijff, S. N., Fiksinski, A., Moss, H., Niarchou, M., Murphy, K. C., Prasad, S. E., Daly, E. M., Gudbrandsen, M., Murphy, C. M., Murphy, D. G., Buzzanca, A., Fabio, F. D., Digilio, M. C., Pontillo, M., Marino, B., Vicari, Stefano, Coleman, K., Cubells, J. F., Ousley, O. Y., Carmel, M., Gothelf, D., Mekori-Domachevsky, E., Michaelovsky, E., Weinberger, R., Weizman, A., Kushan, L., Jalbrzikowski, M., Armando, M., Eliez, S., Sandini, C., Schneider, M., Bena, F. S., Antshel, K. M., Fremont, W., Kates, W. R., Belzeaux, R., Busa, T., Philip, N., Campbell, L. E., Mccabe, K. L., Hooper, S. R., Schoch, K., Shashi, V., Simon, T. J., Tassone, F., Arango, C., Fraguas, D., Garcia-Minaur, S., Morey-Canyelles, J., Rosell, J., Suner, D. H., Raventos-Simic, J., Epstein, M. P., Williams, N. M., Bassett, A. S., Zhao Y., Vicari S. (ORCID:0000-0002-5395-2262), Cleynen, I., Engchuan, W., Hestand, M. S., Heung, T., Holleman, A. M., Johnston, H. R., Monfeuga, T., McDonald-McGinn, D. M., Gur, R. E., Morrow, B. E., Swillen, A., Vorstman, J. A. S., Bearden, C. E., Chow, E. W. C., van den Bree, M., Emanuel, B. S., Vermeesch, J. R., Warren, S. T., Owen, M. J., Chopra, P., Cutler, D. J., Duncan, R., Kotlar, A. V., Mulle, J. G., Voss, A. J., Zwick, M. E., Diacou, A., Golden, A., Guo, T., Lin, J. -R., Wang, T., Zhang, Z., Zhao, Yu Yang, Marshall, C., Merico, D., Jin, A., Lilley, B., Salmons, H. I., Tran, O., Holmans, P., Pardinas, A., Walters, J. T. R., Demaerel, W., Boot, E., Butcher, N. J., Costain, G. A., Lowther, C., Evers, R., van Amelsvoort, T. A. M. J., van Duin, E., Vingerhoets, C., Breckpot, J., Devriendt, K., Vergaelen, E., Vogels, A., Crowley, T. B., Mcginn, D. E., Moss, E. M., Sharkus, R. J., Unolt, M., Zackai, E. H., Calkins, M. E., Gallagher, R. S., Gur, R. C., Tang, S. X., Fritsch, R., Ornstein, C., Repetto, G. M., Breetvelt, E., Duijff, S. N., Fiksinski, A., Moss, H., Niarchou, M., Murphy, K. C., Prasad, S. E., Daly, E. M., Gudbrandsen, M., Murphy, C. M., Murphy, D. G., Buzzanca, A., Fabio, F. D., Digilio, M. C., Pontillo, M., Marino, B., Vicari, Stefano, Coleman, K., Cubells, J. F., Ousley, O. Y., Carmel, M., Gothelf, D., Mekori-Domachevsky, E., Michaelovsky, E., Weinberger, R., Weizman, A., Kushan, L., Jalbrzikowski, M., Armando, M., Eliez, S., Sandini, C., Schneider, M., Bena, F. S., Antshel, K. M., Fremont, W., Kates, W. R., Belzeaux, R., Busa, T., Philip, N., Campbell, L. E., Mccabe, K. L., Hooper, S. R., Schoch, K., Shashi, V., Simon, T. J., Tassone, F., Arango, C., Fraguas, D., Garcia-Minaur, S., Morey-Canyelles, J., Rosell, J., Suner, D. H., Raventos-Simic, J., Epstein, M. P., Williams, N. M., Bassett, A. S., Zhao Y., and Vicari S. (ORCID:0000-0002-5395-2262)

Abstract

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Published
2020

42. Morbidity risk of chromosomal breakpoints in topological domains enriched in non-exonic conserved elements

Author

Bak, M., Fonseca, A., Mehrjouy, M., Rasmussen, M., Halgren, C., Bache, I., Kroisel, P., Midyan, S., Vermeesch, J., Vienna-Morgante, A., Abe, K., Moretti-Ferreira, D., Angelova, L., Rajcan-Separovic, E., Sismani, C., Aristidou, C., Sedlacek, Z., Fagerberg, C., Brondum-Nielsen, K., Vogel, I., Bojesen, A., Ounap, K., Roht, L., Lespinasse, J., Beneteau, C., Kalscheuer, V., Ehmke, N., Daumer-Haas, C., Stefanou, E., Czako, M., Sheth, F., Bonaglia, C., Novelli, A., Fannemel, M., Engelen, J., Travessa, A., Kokalj-Vokac, N., Ramos-Arroyo, M., Martinez, L. R., Guitart, M., Schinzel, A., Silan, F., de Almeida, C., Akkari, Y., Batanian, J., Kim, H., Jacky, P., Tommerup, N., and Consortium, Int Breakpoint Mapping

Published
2019
Full Text
View/download PDF

43. Diagnostic implications of genetic copy number variation in epilepsy plus

Author

Coppola, A., Cellini, E., Stamberger, H., Saarentaus, E., Cetica, V., Lal, D., Djemie, T., Bartnik-Glaska, M., Ceulemans, B., Helen Cross, J., Deconinck, T., Masi, S. D., Dorn, T., Guerrini, R., Hoffman-Zacharska, D., Kooy, F., Lagae, L., Lench, N., Lemke, J. R., Lucenteforte, E., Madia, F., Mefford, H. C., Morrogh, D., Nuernberg, P., Palotie, A., Schoonjans, A. -S., Striano, P., Szczepanik, E., Tostevin, A., Vermeesch, J. R., Van Esch, H., Van Paesschen, W., Waters, J. J., Weckhuysen, S., Zara, F., Jonghe, P. D., Sisodiya, S. M., Marini, C., Lehesjioki, A. -E., Craiu, D., Talvik, T., Caglayan, H., Serratosa, J., Sterbova, K., Moller, R. S., Hjalgrim, H., Lerche, H., Weber, Y., Helbig, I., von Spiczak, S., Barba, C., Bogaerts, A., Boni, A., Galizia, E. C., Chiari, S., Di Gacomo, G., Ferrari, A., Guarducci, S., Giglio, S., Holmgren, P., Leu, C., Melani, F., Novara, F., Pantaleo, M., Peeters, E., Pisano, T., Rosati, A., Sander, J., Schoeler, N., Stankiewicz, P., Striano, S., Suls, A., Traverso, M., Vandeweyer, G., Van Dijck, A., Zuffardi, O., Coppola, Antonietta, Cellini, Elena, Stamberger, Hannah, Saarentaus, Elmo, Cetica, Valentina, Lal, Denni, Djémié, Tania, Bartnik-Glaska, Magdalena, Ceulemans, Berten, Helen Cross, J., Deconinck, Tine, Masi, Salvatore De, Dorn, Thoma, Guerrini, Renzo, Hoffman-Zacharska, Dorotha, Kooy, Frank, Lagae, Lieven, Lench, Nichola, Lemke, Johannes R., Lucenteforte, Ersilia, Madia, Francesca, Mefford, Heather C., Morrogh, Deborah, Nuernberg, Peter, Palotie, Aarno, Schoonjans, An-Sofie, Striano, Pasquale, Szczepanik, Elzbieta, Tostevin, Anna, Vermeesch, Joris R., Van Esch, Hilde, Van Paesschen, Wim, Waters, Jonathan J, Weckhuysen, Sarah, Zara, Federico, Jonghe, Peter De, Sisodiya, Sanjay M., Marini, Carla, Lehesjioki, Anna-Elina, Craiu, Dana, Talvik, Tiina, Caglayan, Hande, Serratosa, Jose, Sterbova, Katalin, Møller, Rikke S., Hjalgrim, Helle, Lerche, Holger, Weber, Yvonne, Helbig, Ingo, von Spiczak, Sarah, Barba, Carmen, Bogaerts, Anneleen, Boni, Antonella, Galizia, Elisabeth Caruana, Chiari, Sara, Di Gacomo, Gianpiero, Ferrari, Annarita, Guarducci, Silvia, Giglio, Sabrina, Holmgren, Philip, Leu, Costin, Melani, Federico, Novara, Francesca, Pantaleo, Marilena, Peeters, Elke, Pisano, Tiziana, Rosati, Anna, Sander, Josemir, Schoeler, Natasha, Stankiewicz, Pawel, Striano, Salvatore, Suls, Arvid, Traverso, Monica, Vandeweyer, Geert, Van Dijck, Anke, and Zuffardi, Orsetta

Subjects
epilepsy gene, Epilepsy, DNA Copy Number Variations, Genotype, Comorbidity, array CGH, copy number variants, epilepsy genes, SNP array, Phenotype, Neurology, mental disorders, Full‐length Original Research, Humans, copy number variant, Genetic Predisposition to Disease, Neurology (clinical)
Abstract

Summary Objective Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available. Methods We assembled a cohort of 1255 patients with preexisting array comparative genomic hybridization or single nucleotide polymorphism array based CNV data. All patients had “epilepsy plus,” defined as epilepsy with comorbid features, including intellectual disability, psychiatric symptoms, and other neurological and nonneurological features. CNV classification was conducted using a systematic filtering workflow adapted to epilepsy. Results Of 1097 patients remaining after genetic data quality control, 120 individuals (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 individuals (1.7%) carried at least one autosomal CNV classified as possibly pathogenic. Eleven patients (1%) carried more than one (possibly) pathogenic CNV. We identified CNVs covering recently reported (HNRNPU) or emerging (RORB) epilepsy genes, and further delineated the phenotype associated with mutations of these genes. Additional novel epilepsy candidate genes emerge from our study. Comparing phenotypic features of pathogenic CNV carriers to those of noncarriers of pathogenic CNVs, we show that patients with nonneurological comorbidities, especially dysmorphism, were more likely to carry pathogenic CNVs (odds ratio = 4.09, confidence interval = 2.51‐6.68; P = 2.34 × 10−9). Meta‐analysis including data from published control groups showed that the presence or absence of epilepsy did not affect the detected frequency of CNVs. Significance The use of a specifically adapted workflow enabled identification of pathogenic autosomal CNVs in 10.9% of patients with epilepsy plus, which rose to 12.7% when we also considered possibly pathogenic CNVs. Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection. Collaborative large‐scale CNV reanalysis leads to novel declaration of pathogenicity in unexplained cases and can promote discovery of promising candidate epilepsy genes.

Published
2019

44. Missense variants in TAF1 and developmental phenotypes: Challenges of determining pathogenicity

Author

Cheng, H., Capponi, S., Wakeling, E., Marchi, E., Li, Q., Zhao, M., Weng, C., Stefan, P.G., Ahlfors, H., Kleyner, R., Rope, A., Lumaka, A., Lukusa, P., Devriendt, K., Vermeesch, J., Posey, J.E., Palmer, E.E., Murray, L., Leon, E., Diaz, J., Worgan, L., Mallawaarachchi, A., Vogt, J., Munnik, S.A., Dreyer, L., Baynam, G., Ewans, L., Stark, Z., Lunke, S., Gonçalves, A.R., Soares, G., Oliveira, J., Fassi, E., Willing, M., Waugh, J.L., Faivre, L., Riviere, J‐B, Moutton, S., Mohammed, S., Payne, K., Walsh, L., Begtrup, A., Guillen Sacoto, M.J., Douglas, G., Alexander, N., Buckley, M.F., Mark, P.R., Adès, L.C., Sandaradura, S.A., Lupski, J.R., Roscioli, T., Agrawal, P.B., Kline, A.D., Wang, K., Timmers, H.T.M., Lyon, G.J., Cheng, H., Capponi, S., Wakeling, E., Marchi, E., Li, Q., Zhao, M., Weng, C., Stefan, P.G., Ahlfors, H., Kleyner, R., Rope, A., Lumaka, A., Lukusa, P., Devriendt, K., Vermeesch, J., Posey, J.E., Palmer, E.E., Murray, L., Leon, E., Diaz, J., Worgan, L., Mallawaarachchi, A., Vogt, J., Munnik, S.A., Dreyer, L., Baynam, G., Ewans, L., Stark, Z., Lunke, S., Gonçalves, A.R., Soares, G., Oliveira, J., Fassi, E., Willing, M., Waugh, J.L., Faivre, L., Riviere, J‐B, Moutton, S., Mohammed, S., Payne, K., Walsh, L., Begtrup, A., Guillen Sacoto, M.J., Douglas, G., Alexander, N., Buckley, M.F., Mark, P.R., Adès, L.C., Sandaradura, S.A., Lupski, J.R., Roscioli, T., Agrawal, P.B., Kline, A.D., Wang, K., Timmers, H.T.M., and Lyon, G.J.

Abstract

We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability [ID] syndrome) (MIM# 300966) caused by pathogenic variants involving the X‐linked gene TATA‐box binding protein associated factor 1 (TAF1), which participates in RNA polymerase II transcription. The initial study reported 11 families, and the syndrome was defined as presenting early in life with hypotonia, facial dysmorphia, and developmental delay that evolved into ID and/or autism spectrum disorder. We have now identified an additional 27 families through a genotype‐first approach. Familial segregation analysis, clinical phenotyping, and bioinformatics were capitalized on to assess potential variant pathogenicity, and molecular modeling was performed for those variants falling within structurally characterized domains of TAF1. A novel phenotypic clustering approach was also applied, in which the phenotypes of affected individuals were classified using 51 standardized Human Phenotype Ontology terms. Phenotypes associated with TAF1 variants show considerable pleiotropy and clinical variability, but prominent among previously unreported effects were brain morphological abnormalities, seizures, hearing loss, and heart malformations. Our allelic series broadens the phenotypic spectrum of the TAF1/MRXS33 ID syndrome and the range of TAF1 molecular defects in humans. It also illustrates the challenges for determining the pathogenicity of inherited missense variants, particularly for a gene mapping to chromosome X.

Published
2019

45. CRISPR/Cas9-mediated editing for dominant genetic disorders: efficient excision of trinucleotide repeat expansion in myotonic dystrophy

Author

Dastidar, S., Ardui, S., Singh, K., Nair, N., Fu, Y., Reyon, D., Samara, E., Gerli, M. F. M., Klein, A. F., DeSchrijver, W., Majumdar, D., Tipanee, J., Seneca, S., Tulalamba, W., Wang, H., Chai, Y. C., In't Veld, P., Furling, D., Tedesco, F. S., Vermeesch, J. R., Joung, J. K., Chuah, M. K., VandenDriessche, T., Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Division of Gene Therapy & Regenerative Medicine, Physics, Medicine and Pharmacy academic/administration, Faculty of Sciences and Bioengineering Sciences, Clinical sciences, Medical Genetics, Reproduction and Genetics, Experimental Pathology, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Vrije Universiteit Brussel

Published
2017

46. Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3

Author

Guo, T, Repetto, GM, McDonald McGinn, DM, Chung, JH, Nomaru, H, Campbell, CL, Blonska, A, Bassett, AS, Chow, EWC, Mlynarski, EE, Swillen, A, Vermeesch, J, Devriendt, K, Gothelf, D, Carmel, M, Michaelovsky, E, Schneider, M, Eliez, S, Antonarakis, SE, Coleman, K, Tomita-Mitchell, A, Mitchell, ME, Digilio, MC, Dallapiccola, B, Marino, B, Philip, N, Busa, T, Kushan-Wells, L, Bearden, CE, Piotrowicz, M, Hawuła, W, Roberts, AE, Tassone, F, Simon, TJ, Van Duin, EDA, Van Amelsvoort, TA, Kates, WR, Zackai, E, Johnston, HR, Cutler, DJ, Agopian, AJ, Goldmuntz, E, Mitchell, LE, Wang, T, Emanuel, BS, and Morrow, BE

Subjects
International 22q11.2 Consortium/Brain and Behavior Consortium
Abstract

© 2017 The Authors. Background - The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906) have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot (TOF), comprising the largest subset of severe congenital heart disease in the cohort. Methods and Results - To identify common genetic variants associated with TOF in individuals with 22q11.2DS, we performed a genome-wide association study using Affymetrix 6.0 array and imputed genotype data. In our cohort, TOF was significantly associated with a genotyped single-nucleotide polymorphism (rs12519770, P=2.98×10-8) in an intron of the adhesion GPR98 (G-protein-coupled receptor V1) gene on chromosome 5q14.3. There was also suggestive evidence of association between TOF and several additional single-nucleotide polymorphisms in this region. Some genome-wide significant loci in introns or noncoding regions could affect regulation of genes nearby or at a distance. On the basis of this possibility, we examined existing Hi-C chromatin conformation data to identify genes that might be under shared transcriptional regulation within the region on 5q14.3. There are 6 genes in a topologically associated domain of chromatin with GPR98, including MEF2C (Myocyte-specific enhancer factor 2C). MEF2C is the only gene that is known to affect heart development in mammals and might be of interest with respect to 22q11.2DS. Conclusions - In conclusion, common variants may contribute to TOF in 22q11.2DS and may function in cardiac outflow tract development.

Published
2017
Full Text
View/download PDF

47. Unbiased genomewide screening of circulating plasma DNA for cancer detection

Author

Lenaerts, L., primary, Brison, N., additional, Neofytou, M., additional, Che, H., additional, Dehaspe, L., additional, Verheecke, M., additional, Maggen, C., additional, Dewaele, B., additional, Vanderschueren, S., additional, Vandecaveye, V., additional, Vandenberghe, P., additional, Vermeesch, J., additional, and Amant, F., additional

Published
2018
Full Text
View/download PDF

48. Recent developments in genetics and medically-assisted reproduction: from research to clinical applications

Author

European Society of Human Reproduction and Embryology and European Society of Human Genetics, Harper, J C, Aittomäki, K, Borry, P, Cornel, M C, de Wert, G, Dondorp, W, Geraedts, J, Gianaroli, L, Ketterson, K, Liebaers, I, Lundin, K, Mertes, H, Morris, M, Pennings, G, Sermon, K, Spits, C, Soini, S, van Montfoort, A P A, Veiga, A, Vermeesch, J R, Viville, S, Macek, M, RS: GROW - R4 - Reproductive and Perinatal Medicine, RS: CAPHRI - R6 - Promoting Health & Personalised Care, Metamedica, Klinische Genetica, Obstetrie & Gynaecologie, Vriendenkring VUB, Reproduction and Genetics, Medical Genetics, Surgical clinical sciences, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Clinical genetics, Amsterdam Reproduction & Development, APH - Quality of Care, and APH - Personalized Medicine

Subjects
0301 basic medicine, 030219 obstetrics & reproductive medicine, gamete donor anonymity, epigenetics, mitochondrial replacement therapy, female infertility, expanded carrier screening, germline genome editing, male infertility, ESHRE Pages, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, assisted reproductive technology, Medicine and Health Sciences, preimplantation genetic testing, non-invasive prenatal testing
Abstract

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively-parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results