197 results on '"Pierson, Tyler Mark"'
Search Results
2. Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning
- Author
-
Abad, Clemer, Robayo, Maria C., Muñiz-Moreno, Maria del Mar, Bernardi, Maria T., Otero, Maria G., Kosanovic, Christina, Griswold, Anthony J., Pierson, Tyler Mark, Walz, Katherina, and Young, Juan I.
- Published
- 2024
- Full Text
- View/download PDF
3. Risks and benefits of anesthesia for combined pediatric procedures in the NIH undiagnosed diseases program
- Author
-
Macnamara, Ellen F., Loydpierson, Amelia, Latour, Yvonne L., D'Souza, Precilla, Murphy, Jennifer, Wolfe, Lynne, Estwick, Tyra, Johnston, Jean M., Yang, John, Acosta, Maria T., Lee, Paul R., Pierson, Tyler Mark, Soldatos, Ariane, Toro, Camilo, Markello, Tom, Adams, David R., Gahl, William A., Yousef, Muhammad, and Tifft, Cynthia J.
- Published
- 2023
- Full Text
- View/download PDF
4. De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder
- Author
-
Werren, Elizabeth A., Guxholli, Alba, Jones, Natasha, Wagner, Matias, Hannibal, Iris, Granadillo, Jorge L., Tyndall, Amanda V., Moccia, Amanda, Kuehl, Ryan, Levandoski, Kristin M., Day-Salvatore, Debra L., Wheeler, Marsha, Chong, Jessica X., Bamshad, Michael J., Innes, A. Micheil, Pierson, Tyler Mark, Mackay, Joel P., Bielas, Stephanie L., and Martin, Donna M.
- Published
- 2023
- Full Text
- View/download PDF
5. GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder
- Author
-
Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden Y, Silva, Ana PG, Lee, Hane, Douine, Emilie D, Otero, Maria G, Choi, Andrew, Grand, Katheryn, Taff, Ingrid P, Delgado, Mauricio R, Hajianpour, MJ, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen W, Vergano, Samantha A, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana Berta, Wain, Karen E, Challman, Thomas D, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James J, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren DM, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane A, Hurst, Jane, Fitzpatrick, David R, Morton, Jenny EV, Cox, Helen, Venkateswaran, Sunita, Young, Juan I, Marsh, Eric D, Nelson, Stanley F, Martinez, Julian A, Graham, John M, Kini, Usha, Mackay, Joel P, and Pierson, Tyler Mark
- Subjects
Genetics ,Clinical Research ,Congenital Structural Anomalies ,Brain Disorders ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,2.1 Biological and endogenous factors ,Aetiology ,Child ,Female ,GATA Transcription Factors ,Humans ,Intellectual Disability ,Megalencephaly ,Neurodevelopmental Disorders ,Nucleosomes ,Phenotype ,Pregnancy ,Repressor Proteins ,GATAD2B ,NuRD complex ,apraxia of speech ,chromatin remodeling ,macrocephaly ,Undiagnosed Diseases Network ,GATAD2B ,NuRD complex ,apraxia of speech ,chromatin remodeling ,macrocephaly ,Clinical Sciences ,Genetics & Heredity - Abstract
PurposeDetermination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).MethodsFifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.ResultsSubjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.ConclusionsA consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.
- Published
- 2020
6. Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.
- Author
-
Hengel, Holger, Bosso-Lefèvre, Célia, Grady, George, Szenker-Ravi, Emmanuelle, Li, Hankun, Pierce, Sarah, Lebigot, Élise, Tan, Thong-Teck, Eio, Michelle Y, Narayanan, Gunaseelan, Utami, Kagistia Hana, Yau, Monica, Handal, Nader, Deigendesch, Werner, Keimer, Reinhard, Marzouqa, Hiyam M, Gunay-Aygun, Meral, Muriello, Michael J, Verhelst, Helene, Weckhuysen, Sarah, Mahida, Sonal, Naidu, Sakkubai, Thomas, Terrence G, Lim, Jiin Ying, Tan, Ee Shien, Haye, Damien, Willemsen, Michèl AAP, Oegema, Renske, Mitchell, Wendy G, Pierson, Tyler Mark, Andrews, Marisa V, Willing, Marcia C, Rodan, Lance H, Barakat, Tahsin Stefan, van Slegtenhorst, Marjon, Gavrilova, Ralitza H, Martinelli, Diego, Gilboa, Tal, Tamim, Abdullah M, Hashem, Mais O, AlSayed, Moeenaldeen D, Abdulrahim, Maha M, Al-Owain, Mohammed, Awaji, Ali, Mahmoud, Adel AH, Faqeih, Eissa A, Asmari, Ali Al, Algain, Sulwan M, Jad, Lamyaa A, Aldhalaan, Hesham M, Helbig, Ingo, Koolen, David A, Riess, Angelika, Kraegeloh-Mann, Ingeborg, Bauer, Peter, Gulsuner, Suleyman, Stamberger, Hannah, Ng, Alvin Yu Jin, Tang, Sha, Tohari, Sumanty, Keren, Boris, Schultz-Rogers, Laura E, Klee, Eric W, Barresi, Sabina, Tartaglia, Marco, Mor-Shaked, Hagar, Maddirevula, Sateesh, Begtrup, Amber, Telegrafi, Aida, Pfundt, Rolph, Schüle, Rebecca, Ciruna, Brian, Bonnard, Carine, Pouladi, Mahmoud A, Stewart, James C, Claridge-Chang, Adam, Lefeber, Dirk J, Alkuraya, Fowzan S, Mathuru, Ajay S, Venkatesh, Byrappa, Barycki, Joseph J, Simpson, Melanie A, Jamuar, Saumya S, Schöls, Ludger, and Reversade, Bruno
- Subjects
Organoids ,Animals ,Zebrafish ,Humans ,Epilepsy ,Syndrome ,Oxidoreductases ,Pedigree ,Kinetics ,Genes ,Recessive ,Alleles ,Adolescent ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Protein Domains ,Loss of Function Mutation ,Preschool ,Genes ,Recessive - Abstract
Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.
- Published
- 2020
7. Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy
- Author
-
Souza, Ivana A, Gandini, Maria A, Zhang, Fang-Xiong, Mitchell, Wendy G, Matsumoto, Joyce, Lerner, Jason, Pierson, Tyler Mark, and Zamponi, Gerald W
- Subjects
Epilepsy ,Neurodegenerative ,Brain Disorders ,Neurosciences ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Biophysical Phenomena ,Calcium Channels ,T-Type ,Child ,Epilepsy ,Generalized ,Female ,Humans ,Infant ,Infant ,Newborn ,Mutation ,Cav3 ,2 ,T-type ,Seizure ,Cav3.2 ,Medical and Health Sciences ,Neurology & Neurosurgery - Abstract
Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.
- Published
- 2019
8. Functional effects of disease-associated variants reveal that the S1–M1 linker of the NMDA receptor critically controls channel opening
- Author
-
Xie, Lingling, McDaniel, Miranda J., Perszyk, Riley E., Kim, Sukhan, Cappuccio, Gerarda, Shapiro, Kevin A., Muñoz-Cabello, Beatriz, Sanchez-Lara, Pedro A., Grand, Katheryn, Zhang, Jing, Nocilla, Kelsey A., Sheikh, Rehan, Armengol, Lluis, Romano, Roberta, Pierson, Tyler Mark, Yuan, Hongjie, Myers, Scott J., and Traynelis, Stephen F.
- Published
- 2023
- Full Text
- View/download PDF
9. Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation
- Author
-
Tulli, Susanna, Del Bondio, Andrea, Baderna, Valentina, Mazza, Davide, Codazzi, Franca, Pierson, Tyler Mark, Ambrosi, Alessandro, Nolte, Dagmar, Goizet, Cyril, Toro, Camilo, Baets, Jonathan, Deconinck, Tine, DeJonghe, Peter, Mandich, Paola, Casari, Giorgio, and Maltecca, Francesca
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,ATP-Dependent Proteases ,ATPases Associated with Diverse Cellular Activities ,Animals ,Calcium ,Fibroblasts ,Genetic Variation ,HEK293 Cells ,Haploinsufficiency ,Humans ,Metalloendopeptidases ,Mice ,Mice ,Knockout ,Mitochondria ,Models ,Biological ,Protein Binding ,Protein Domains ,Protein Multimerization ,Proteolysis ,Proteostasis ,Stress ,Physiological ,Transcriptional Activation ,genetics ,molecular genetics ,movement disorders ,mitochondria ,cell biology ,Medical and Health Sciences ,Genetics & Heredity ,Genetics ,Clinical sciences - Abstract
BACKGROUND:Spinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date. METHODS:We derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2+/- HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2 -/- murine fibroblasts. RESULTS:We found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells. CONCLUSION:Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2+/- cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.
- Published
- 2019
10. Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy
- Author
-
Otero, Maria G, Tiongson, Emmanuelle, Diaz, Frank, Haude, Katrina, Panzer, Karin, Collier, Ashley, Kim, Jaemin, Adams, David, Tifft, Cynthia J, Cui, Hong, Zamora, Francisca Millian, Au, Margaret G, Graham, John M, Buckley, David J, Lewis, Richard, Toro, Camilo, Bai, Renkui, Turner, Lesley, Mathews, Katherine D, Gahl, William, and Pierson, Tyler Mark
- Subjects
Clinical and Health Psychology ,Biomedical and Clinical Sciences ,Neurosciences ,Psychology ,Peripheral Neuropathy ,Clinical Research ,Genetics ,Neurodegenerative ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Adolescent ,Adult ,Ataxia ,Child ,Dysarthria ,Electron Transport Complex IV ,Female ,Hereditary Sensory and Autonomic Neuropathies ,Humans ,Male ,Pedigree ,Phenotype ,Clinical Sciences ,Clinical and health psychology - Abstract
COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
- Published
- 2019
11. Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations
- Author
-
Tripathy, Ratna, Leca, Ines, van Dijk, Tessa, Weiss, Janneke, van Bon, Bregje W, Sergaki, Maria Christina, Gstrein, Thomas, Breuss, Martin, Tian, Guoling, Bahi-Buisson, Nadia, Paciorkowski, Alexander R, Pagnamenta, Alistair T, Wenninger-Weinzierl, Andrea, Martinez-Reza, Maria Fernanda, Landler, Lukas, Lise, Stefano, Taylor, Jenny C, Terrone, Gaetano, Vitiello, Giuseppina, Del Giudice, Ennio, Brunetti-Pierri, Nicola, D’Amico, Alessandra, Reymond, Alexandre, Voisin, Norine, Bernstein, Jonathan A, Farrelly, Ellyn, Kini, Usha, Leonard, Thomas A, Valence, Stéphanie, Burglen, Lydie, Armstrong, Linlea, Hiatt, Susan M, Cooper, Gregory M, Aldinger, Kimberly A, Dobyns, William B, Mirzaa, Ghayda, Pierson, Tyler Mark, Baas, Frank, Chelly, Jamel, Cowan, Nicholas J, and Keays, David Anthony
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Rare Diseases ,Pediatric ,Genetics ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Congenital Structural Anomalies ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Agenesis of Corpus Callosum ,Animals ,Animals ,Newborn ,Apoptosis ,Brain ,Cells ,Cultured ,Cerebellum ,Child ,Developmental Disabilities ,Disease Models ,Animal ,Embryo ,Mammalian ,Female ,Gene Expression Regulation ,Developmental ,Humans ,Male ,Malformations of Cortical Development ,Mice ,Mice ,Inbred C57BL ,Mice ,Knockout ,Microtubule-Associated Proteins ,Mutation ,Nerve Tissue Proteins ,Nervous System Malformations ,PAX6 Transcription Factor ,MAST1 ,cerebellar hypoplasia ,corpus callosum ,microdeletion ,microtubules ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Corpus callosum malformations are associated with a broad range of neurodevelopmental diseases. We report that de novo mutations in MAST1 cause mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCC-CH-CM) in the absence of megalencephaly. We show that MAST1 is a microtubule-associated protein that is predominantly expressed in post-mitotic neurons and is present in both dendritic and axonal compartments. We further show that Mast1 null animals are phenotypically normal, whereas the deletion of a single amino acid (L278del) recapitulates the distinct neurological phenotype observed in patients. In animals harboring Mast1 microdeletions, we find that the PI3K/AKT3/mTOR pathway is unperturbed, whereas Mast2 and Mast3 levels are diminished, indicative of a dominant-negative mode of action. Finally, we report that de novo MAST1 substitutions are present in patients with autism and microcephaly, raising the prospect that mutations in this gene give rise to a spectrum of neurodevelopmental diseases.
- Published
- 2018
12. GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function
- Author
-
Chen, Wenjuan, Shieh, Christine, Swanger, Sharon A, Tankovic, Anel, Au, Margaret, McGuire, Marianne, Tagliati, Michele, Graham, John M, Madan-Khetarpal, Suneeta, Traynelis, Stephen F, Yuan, Hongjie, and Pierson, Tyler Mark
- Subjects
Brain Disorders ,Mental Health ,Neurosciences ,Neurological ,Adult ,Cell Membrane ,Child ,Female ,Glycine ,Humans ,Intellectual Disability ,Male ,Mutation ,Nerve Tissue Proteins ,Neurons ,Protein Transport ,Receptors ,N-Methyl-D-Aspartate ,Recombinant Proteins ,Genetics ,Clinical Sciences ,Genetics & Heredity - Abstract
N-methyl-d-aspartate receptors (NMDARs) play important roles in brain development and neurological disease. We report two individuals with similar dominant de novo GRIN1 mutations (c.1858 G>A and c.1858 G>C; both p.G620R). Both individuals presented at birth with developmental delay and hypotonia associated with behavioral abnormalities and stereotypical movements. Recombinant NMDARs containing the mutant GluN1-G620R together with either GluN2A or GluN2B were evaluated for changes in their trafficking to the plasma membrane and their electrophysiological properties. GluN1-G620R/GluN2A complexes showed a mild reduction in trafficking, a ~2-fold decrease in glutamate and glycine potency, a strong decrease in sensitivity to Mg2+ block, and a significant reduction of current responses to a maximal effective concentration of agonists. GluN1-G620R/GluN2B complexes showed significantly reduced delivery of protein to the cell surface associated with similarly altered electrophysiology. These results indicate these individuals may have suffered neurodevelopmental deficits as a result of the decreased presence of GluN1-G620R/GluN2B complexes on the neuronal surface during embryonic brain development and reduced current responses of GluN1-G620R-containing NMDARs after birth. These cases emphasize the importance of comprehensive functional characterization of de novo mutations and illustrates how a combination of several distinct features of NMDAR expression, trafficking and function can be present and influence phenotype.
- Published
- 2017
13. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling
- Author
-
Pena, Loren, Shashi, Vandana, Schoch, Kelly, Sullivan, Jennifer A., Acosta, Maria T., Adams, David R., Aday, Aaron, Alejandro, Mercedes E., Allard, Patrick, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Barbouth, Deborah, Batzli, Gabriel F., Beggs, Alan H., Bellen, Hugo J., Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bick, David P., Birch, Camille L., Bivona, Stephanie, Bonnenmann, Carsten, Bonner, Devon, Boone, Braden E., Bostwick, Bret L., Briere, Lauren C., Brokamp, Elly, Brown, Donna M., Brush, Matthew, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Carrasquillo, Olveen, Peter Chang, Ta Chen, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Cope, Heidi, Craigen, William J., D'Souza, Precilla, Dasari, Surendra, Davids, Mariska, Davidson, Jean M., Dayal, Jyoti G., Dell'Angelica, Esteban C., Dhar, Shweta U., Dorrani, Naghmeh, Dorset, Daniel C., Douine, Emilie D., Draper, David D., Dries, Annika M., Duncan, Laura, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Enns, Gregory M., Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Friedman, Noah D., Gahl, William A., Godfrey, Rena A., Goldman, Alica M., Goldstein, David B., Gourdine, Jean-Philippe F., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Haendel, Melissa, Hamid, Rizwan, Hanchard, Neil A., High, Frances, Holm, Ingrid A., Hom, Jason, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jiang, Yong-hui, Johnston, Jean M., Jones, Angela L., Karaviti, Lefkothea, Kelley, Emily G., Koeller, David M., Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Korrick, Susan, Koziura, Mary, Krier, Joel B., Kyle, Jennifer E., Lalani, Seema R., Lam, Byron, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, Lazar, Jozef, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Levy, Shawn E., Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Markello, Thomas C., Marom, Ronit, Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, May, Thomas, McCauley, Jacob, McConkie-Rosell, Allyn, McCormack, Colleen E., McCray, Alexa T., Merker, Jason D., Metz, Thomas O., Might, Matthew, Morava-Kozicz, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nath, Avi, Nelson, Stan F., Newberry, J. Scott, Newman, John H., Nicholas, Sarah K., Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pak, Stephen, Pallais, J. Carl, Palmer, Christina GS., Papp, Jeanette C., Parker, Neil H., Phillips, John A., III, Posey, Jennifer E., Postlethwait, John H., Potocki, Lorraine, Pusey, Barbara N., Renteri, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rowley, Robb K., Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Shakachite, Lisa, Sharma, Prashant, Shields, Kathleen, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Smith, Kevin S., Solnica-Krezel, Lilianna, Spillmann, Rebecca C., Stoler, Joan M., Stong, Nicholas, Sweetser, David A., Tamburro, Cecelia P., Tan, Queenie K.-G., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Urv, Tiina K., Vogel, Tiphanie P., Waggott, Daryl M., Wahl, Colleen E., Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-kai, Wangler, Michael F., Ward, Patricia A., Waters, Katrina M., Webb-Robertson, Bobbie-Jo M., Wegner, Daniel, Westerfield, Monte, Wheeler, Matthew T., Wise, Anastasia L., Wolfe, Lynne A., Woods, Jeremy D., Worthey, Elizabeth A., Yamamoto, Shinya, Yang, John, Yoon, Amanda J., Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Gahl, William, Johnson, Brett V., Kumar, Raman, Oishi, Sabrina, Alexander, Suzy, Kasherman, Maria, Vega, Michelle Sanchez, Ivancevic, Atma, Gardner, Alison, Domingo, Deepti, Corbett, Mark, Parnell, Euan, Yoon, Sehyoun, Oh, Tracey, Lines, Matthew, Lefroy, Henrietta, Kini, Usha, Van Allen, Margot, Grønborg, Sabine, Mercier, Sandra, Küry, Sébastien, Bézieau, Stéphane, Pasquier, Laurent, Raynaud, Martine, Afenjar, Alexandra, Billette de Villemeur, Thierry, Keren, Boris, Désir, Julie, Van Maldergem, Lionel, Marangoni, Martina, Dikow, Nicola, Koolen, David A., VanHasselt, Peter M., Weiss, Marjan, Zwijnenburg, Petra, Sa, Joaquim, Reis, Claudia Falcao, López-Otín, Carlos, Santiago-Fernández, Olaya, Fernández-Jaén, Alberto, Rauch, Anita, Steindl, Katharina, Joset, Pascal, Goldstein, Amy, Madan-Khetarpal, Suneeta, Infante, Elena, Zackai, Elaine, Mcdougall, Carey, Narayanan, Vinodh, Ramsey, Keri, Mercimek-Andrews, Saadet, Pinto e Vairo, Filippo, Pichurin, Pavel N., Ewing, Sarah A., Barnett, Sarah S., Klee, Eric W., Perry, M. Scott, Koenig, Mary Kay, Keegan, Catherine E., Schuette, Jane L., Asher, Stephanie, Perilla-Young, Yezmin, Smith, Laurie D., Bhoj, Elizabeth, Kaplan, Paige, Li, Dong, Oegema, Renske, van Binsbergen, Ellen, van der Zwaag, Bert, Smeland, Marie Falkenberg, Cutcutache, Ioana, Page, Matthew, Armstrong, Martin, Lin, Angela E., Steeves, Marcie A., Hollander, Nicolette den, Hoffer, Mariëtte J.V., Reijnders, Margot R.F., Demirdas, Serwet, Koboldt, Daniel C., Bartholomew, Dennis, Mosher, Theresa Mihalic, Hickey, Scott E., Shieh, Christine, Sanchez-Lara, Pedro A., Graham, John M., Jr., Tezcan, Kamer, Schaefer, G.B., Danylchuk, Noelle R., Asamoah, Alexander, Jackson, Kelly E., Yachelevich, Naomi, Au, Margaret, Pérez-Jurado, Luis A., Kleefstra, Tjitske, Penzes, Peter, Wood, Stephen A., Burne, Thomas, Pierson, Tyler Mark, Piper, Michael, Gécz, Jozef, and Jolly, Lachlan A.
- Published
- 2020
- Full Text
- View/download PDF
14. Cellular Modeling of CLN6 with IPSC-derived Neurons and Glia
- Author
-
Otero, Maria Gabriela, primary, Kim, Jaemin, additional, Kushwaha, Yogesh Kumar, additional, Rajewski, Alex, additional, Nonis, Fabian David, additional, Santiskulvong, Chintda, additional, Bannykh, Serguei I., additional, Oza, Hiral, additional, Farooqi, Hafiz Muhammad Umer, additional, Babros, Madeline, additional, Freeman, Christina, additional, Dupuis, Lucie, additional, Mercimek-Andrews, Saadat, additional, Mendoza-Londono, Roberto, additional, Bresee, Catherine, additional, Adams, David R., additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Khanlou, Negar, additional, Gahl, William A., additional, Salamon, Noriko, additional, and Pierson, Tyler Mark, additional
- Published
- 2024
- Full Text
- View/download PDF
15. Mutation in the sixth immunoglobulin domain of L1CAM is associated with migrational brain anomalies
- Author
-
Shieh, Christine, Moser, Franklin, Graham, John M, Watiker, Valerie, and Pierson, Tyler Mark
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Neurosciences ,Pediatric ,Congenital Structural Anomalies ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Clinical sciences - Abstract
ObjectiveTo describe the phenotype of a patient with classical features of X-linked L1 syndrome associated with novel brain malformations.MethodsDiagnostic analysis included physical and dysmorphology examinations, MRI of the brain, and exome sequencing of the family trio.ResultsWe report a 2.5-year-old boy with developmental delay, dysmorphic facies, and adducted thumbs. MRI of the brain showed a truncated corpus callosum and periventricular heterotopias associated with polymicrogyria (PMG). Variant segregation analysis with exome sequencing discovered a novel maternally derived hemizygous variant in exon 14 of the L1CAM gene (c.1759 G>C; p.G587R).ConclusionsThis novel L1CAM mutation was located in the protein's sixth immunoglobin domain and involved glycine-587, a key residue in the structure of L1CAM because of its interactions with lysine-606, which indicates that any mutation at this site would likely affect the secondary structure and function of the protein. The replacement of the small nonpolar glycine residue with a large basic arginine would have an even more dramatic result. The presentation of periventricular nodular heterotopias with overlying PMG is very uncommon, and its association with L1CAM may provide insight into other similar cases. Furthermore, this presentation indicates the important role that L1CAM plays in neuronal migration and brain development and extends the phenotype associated with L1CAM-associated disorders.
- Published
- 2015
16. Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A
- Author
-
Zhu, Peng-Peng, Denton, Kyle R, Pierson, Tyler Mark, Li, Xue-Jun, and Blackstone, Craig
- Subjects
Stem Cell Research - Embryonic - Human ,Stem Cell Research ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Neurosciences ,Neurodegenerative ,Underpinning research ,Aetiology ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Neurological ,Amino Acid Sequence ,Animals ,Axons ,Cell Differentiation ,Cell Line ,Child ,Preschool ,DNA Mutational Analysis ,Female ,GTP-Binding Proteins ,Heterozygote ,Humans ,Induced Pluripotent Stem Cells ,Membrane Proteins ,Models ,Molecular ,Molecular Sequence Data ,Mutation ,Neurons ,Protein Conformation ,Protein Transport ,Sequence Alignment ,Spastic Paraplegia ,Hereditary ,Tubulin Modulators ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Hereditary spastic paraplegias are a large, diverse group of neurological disorders (SPG1-71) with the unifying feature of prominent lower extremity spasticity, owing to a length-dependent axonopathy of corticospinal motor neurons. The most common early-onset form of pure, autosomal dominant hereditary spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1 GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER network. We have identified a p.Pro342Ser mutation in a young girl with pure SPG3A. This residue is in a critical hinge region of atlastin-1 between its GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin orthologs. We produced induced pluripotent stem cells from skin fibroblasts and differentiated these into forebrain neurons to generate a human neuronal model for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for mitochondrial distribution and function within cells, and SPG3A neurons showed alterations in mitochondrial motility. Even so, it is not clear whether this change is involved in disease pathogenesis. The SPG3A axon growth defects could be rescued with microtubule-binding agents, emphasizing the importance of tubular ER interactions with the microtubule cytoskeleton in hereditary spastic paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A neurons may represent a particularly attractive target for suppression in screens for novel pharmacologic agents.
- Published
- 2014
17. TUBB4A de novo mutations cause isolated hypomyelination
- Author
-
Pizzino, Amy, Pierson, Tyler Mark, Guo, Yiran, Helman, Guy, Fortini, Sebastian, Guerrero, Kether, Saitta, Sulagna, Murphy, Jennifer Louise Patrick, Padiath, Quasar, Xie, Yi, Hakonarson, Hakon, Xu, Xun, Funari, Tara, Fox, Michelle, Taft, Ryan J, van der Knaap, Marjo S, Bernard, Geneviève, Schiffmann, Raphael, Simons, Cas, and Vanderver, Adeline
- Subjects
Pediatric ,Congenital Structural Anomalies ,Neurosciences ,Brain Disorders ,Genetics ,Clinical Research ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Adolescent ,Atrophy ,Basal Ganglia ,Cerebellum ,Child ,Child ,Preschool ,Exome ,Female ,Hereditary Central Nervous System Demyelinating Diseases ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Mutation ,Phenotype ,Registries ,Tubulin ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveWe present a series of unrelated patients with isolated hypomyelination, with or without mild cerebellar atrophy, and de novo TUBB4A mutations.MethodsPatients in 2 large institutional review board-approved leukodystrophy bioregistries at Children's National Medical Center and Montreal Children's Hospital with similar MRI features had whole-exome sequencing performed. MRIs and clinical information were reviewed.ResultsFive patients who presented with hypomyelination without the classic basal ganglia abnormalities were found to have novel TUBB4A mutations through whole-exome sequencing. Clinical and imaging characteristics were reviewed suggesting a spectrum of clinical manifestations.ConclusionHypomyelinating leukodystrophies remain a diagnostic challenge with a large percentage of unresolved cases. This finding expands the phenotype of TUBB4A-related hypomyelinating conditions beyond hypomyelination with atrophy of the basal ganglia and cerebellum. TUBB4A mutation screening should be considered in cases of isolated hypomyelination or hypomyelination with nonspecific cerebellar atrophy.
- Published
- 2014
18. Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11
- Author
-
Renvoisé, Benoît, Chang, Jaerak, Singh, Rajat, Yonekawa, Sayuri, FitzGibbon, Edmond J, Mankodi, Ami, Vanderver, Adeline, Schindler, Alice B, Toro, Camilo, Gahl, William A, Mahuran, Don J, Blackstone, Craig, and Pierson, Tyler Mark
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Acquired Cognitive Impairment ,Rare Diseases ,Brain Disorders ,Neurodegenerative ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Clinical Sciences ,Clinical and health psychology - Abstract
ObjectiveHereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.MethodsWe describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.ResultsFibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent.InterpretationEmerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26-/- mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction.
- Published
- 2014
19. GRIN2A mutation and early‐onset epileptic encephalopathy: personalized therapy with memantine
- Author
-
Pierson, Tyler Mark, Yuan, Hongjie, Marsh, Eric D, Fuentes-Fajardo, Karin, Adams, David R, Markello, Thomas, Golas, Gretchen, Simeonov, Dimitre R, Holloman, Conisha, Tankovic, Anel, Karamchandani, Manish M, Schreiber, John M, Mullikin, James C, Tifft, Cynthia J, Toro, Camilo, Boerkoel, Cornelius F, Traynelis, Stephen F, and Gahl, William A
- Subjects
Brain Disorders ,Genetics ,Neurosciences ,Biotechnology ,Neurodegenerative ,Pediatric ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Good Health and Well Being ,PhD for the NISC Comparative Sequencing Program ,Clinical Sciences - Abstract
ObjectiveEarly-onset epileptic encephalopathies have been associated with de novo mutations of numerous ion channel genes. We employed techniques of modern translational medicine to identify a disease-causing mutation, analyze its altered behavior, and screen for therapeutic compounds to treat the proband.MethodsThree modern translational medicine tools were utilized: 1) high-throughput sequencing technology to identify a novel de novo mutation; 2) in vitro expression and electrophysiology assays to confirm the variant protein's dysfunction; and 3) screening of existing drug libraries to identify potential therapeutic compounds.ResultsA de novo GRIN2A missense mutation (c.2434C>A; p.L812M) increased the charge transfer mediated by NMDA receptors containing the mutant GluN2A-L812M subunit. In vitro analysis with NMDA receptor blockers indicated that GLuN2A-L812M-containing NMDARs retained their sensitivity to the use-dependent channel blocker memantine; while screening of a previously reported GRIN2A mutation (N615K) with these compounds produced contrasting results. Consistent with these data, adjunct memantine therapy reduced our proband's seizure burden.InterpretationThis case exemplifies the potential for personalized genomics and therapeutics to be utilized for the early diagnosis and treatment of infantile-onset neurological disease.
- Published
- 2014
20. De novo and biallelic DEAF1 variants cause a phenotypic spectrum
- Author
-
Nabais Sá, Maria J., Jensik, Philip J., McGee, Stacey R., Parker, Michael J., Lahiri, Nayana, McNeil, Evan P., Kroes, Hester Y., Hagerman, Randi J., Harrison, Rachel E., Montgomery, Tara, Splitt, Miranda, Palmer, Elizabeth E., Sachdev, Rani K., Mefford, Heather C., Scott, Abbey A., Martinez-Agosto, Julian A., Lorenz, Rüdiger, Orenstein, Naama, Berg, Jonathan N., Amiel, Jeanne, Heron, Delphine, Keren, Boris, Cobben, Jan-Maarten, Menke, Leonie A., Marco, Elysa J., Graham, Jr, John M., Pierson, Tyler Mark, Karimiani, Ehsan Ghayoor, Maroofian, Reza, Manzini, M. Chiara, Cauley, Edmund S., Colombo, Roberto, Odent, Sylvie, Dubourg, Christele, Phornphutkul, Chanika, de Brouwer, Arjan P. M., de Vries, Bert B. A., and Vulto-vanSilfhout, Anneke T.
- Published
- 2019
- Full Text
- View/download PDF
21. A neurodevelopmental disorder associated with an activating de novo missense variant in ARF1
- Author
-
Ishida, Morié, primary, Otero, María G, additional, Freeman, Christina, additional, Sánchez-Lara, Pedro A, additional, Guardia, Carlos M, additional, Pierson, Tyler Mark, additional, and Bonifacino, Juan S, additional
- Published
- 2022
- Full Text
- View/download PDF
22. Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy
- Author
-
Schartner, Vanessa, Romero, Norma B., Donkervoort, Sandra, Treves, Susan, Munot, Pinki, Pierson, Tyler Mark, Dabaj, Ivana, Malfatti, Edoardo, Zaharieva, Irina T., Zorzato, Francesco, Abath Neto, Osorio, Brochier, Guy, Lornage, Xavière, Eymard, Bruno, Taratuto, Ana Lía, Böhm, Johann, Gonorazky, Hernan, Ramos-Platt, Leigh, Feng, Lucy, Phadke, Rahul, Bharucha-Goebel, Diana X., Sumner, Charlotte Jane, Bui, Mai Thao, Lacene, Emmanuelle, Beuvin, Maud, Labasse, Clémence, Dondaine, Nicolas, Schneider, Raphael, Thompson, Julie, Boland, Anne, Deleuze, Jean-François, Matthews, Emma, Pakleza, Aleksandra Nadaj, Sewry, Caroline A., Biancalana, Valérie, Quijano-Roy, Susana, Muntoni, Francesco, Fardeau, Michel, Bönnemann, Carsten G., and Laporte, Jocelyn
- Published
- 2017
- Full Text
- View/download PDF
23. Familial Bainbridge‐Ropers syndrome: Report of familial ASXL3 inheritance and a milder phenotype
- Author
-
Schirwani, Schaida, primary, Woods, Emily, additional, Koolen, David A., additional, Ockeloen, Charlotte W., additional, Lynch, Sally Ann, additional, Kavanagh, Karl, additional, Graham, John M., additional, Grand, Katheryn, additional, Pierson, Tyler Mark, additional, Chung, Jeffrey M., additional, and Balasubramanian, Meena, additional
- Published
- 2022
- Full Text
- View/download PDF
24. Novel SNP array analysis and exome sequencing detect a homozygous exon 7 deletion of MEGF10 causing early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)
- Author
-
Pierson, Tyler Mark, Markello, Thomas, Accardi, John, Wolfe, Lynne, Adams, David, Sincan, Murat, Tarazi, Noor M., Fajardo, Karin Fuentes, Cherukuri, Praveen F., Bajraktari, Ilda, Meilleur, Katy G., Donkervoort, Sandra, Jain, Mina, Hu, Ying, Lehky, Tanya J., Cruz, Pedro, Mullikin, James C., Bonnemann, Carsten, Gahl, William A., Boerkoel, Cornelius F., and Tifft, Cynthia J.
- Published
- 2013
- Full Text
- View/download PDF
25. A neurodevelopmental disorder associated with an activating de novo missense variant in ARF1.
- Author
-
Ishida, Morié, Otero, María G, Freeman, Christina, Sánchez-Lara, Pedro A, Guardia, Carlos M, Pierson, Tyler Mark, and Bonifacino, Juan S
- Published
- 2023
- Full Text
- View/download PDF
26. Familial Bainbridge‐Ropers syndrome: Report of familial ASXL3 inheritance and a milder phenotype.
- Author
-
Schirwani, Schaida, Woods, Emily, Koolen, David A., Ockeloen, Charlotte W., Lynch, Sally Ann, Kavanagh, Karl, Graham, John M., Grand, Katheryn, Pierson, Tyler Mark, Chung, Jeffrey M., and Balasubramanian, Meena
- Abstract
De novo truncating and splicing pathogenic variants in the Additional Sex Combs‐Like 3 (ASXL3) gene are known to cause neurodevelopmental delay, intellectual disability, behavioral difficulties, hypotonia, feeding problems and characteristic facial features. We previously reported 45 patients with ASXL3‐related disorder including three individuals with a familial variant. Here we report the detailed clinical and molecular characteristics of these three families with inherited ASXL3‐related disorder. First, a father and son with c.2791_2792del p.Gln931fs pathogenic variant. The second, a mother, daughter and son with c.4534C > T, p.Gln1512Ter pathogenic variant. The third, a mother and her daughter with c.4441dup, p.Leu1481fs maternally inherited pathogenic variant. This report demonstrates intrafamilial phenotypic heterogeneity and confirms heritability of ASXL3‐related disorder. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
27. Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- Author
-
Wiessner, Manuela, Maroofian, Reza, Ni, Meng-Yuan, Pedroni, Andrea, Muller, Juliane S., Stucka, Rolf, Beetz, Christian, Efthymiou, Stephanie, Santorelli, Filippo M., Alfares, Ahmed A., Zhu, Changlian, Meszarosova, Anna Uhrova, Alehabib, Elham, Bakhtiari, Somayeh, Janecke, Andreas R., Otero, Maria Gabriela, Chen, Jin Yun Helen, Peterson, James T., Strom, Tim M., De Jonghe, Peter, Deconinck, Tine, De Ridder, Willem, De Winter, Jonathan, Pasquariello, Rossella, Ricca, Ivana, Alfadhel, Majid, van de Warrenburg, Bart P., Portier, Ruben, Bergmann, Carsten, Firouzabadi, Saghar Ghasemi, Jin, Sheng Chih, Bilguvar, Kaya, Hamed, Sherifa, Abdelhameed, Mohammed, Haridy, Nourelhoda A., Maqbool, Shazia, Rahman, Fatima, Anwar, Najwa, Carmichael, Jenny, Pagnamenta, Alistair, Wood, Nick W., Mau-Them, Frederic Tran, Haack, Tobias, Di Rocco, Maja, Ceccherini, Isabella, Iacomino, Michele, Zara, Federico, Salpietro, Vincenzo, Scala, Marcello, Rusmini, Marta, Xu, Yiran, Wang, Yinghong, Suzuki, Yasuhiro, Koh, Kishin, Nan, Haitian, Ishiura, Hiroyuki, Tsuji, Shoji, Lambert, Laetitia, Schmitt, Emmanuelle, Lacaze, Elodie, Kupper, Hanna, Dredge, David, Skraban, Cara, Goldstein, Amy, Willis, Mary J. H., Grand, Katheryn, Graham, John M., Lewis, Richard A., Millan, Francisca, Duman, Ozgur, Dundar, Nihal, Uyanik, Gokhan, Schols, Ludger, Nurnberg, Peter, Nurnberg, Gudrun, Bordes, Andrea Catala, Seeman, Pavel, Kuchar, Martin, Darvish, Hossein, Rebelo, Adriana, Boucanova, Filipa, Medard, Jean-Jacques, Chrast, Roman, Auer-Grumbach, Michaela, Alkuraya, Fowzan S., Shamseldin, Hanan, Al Tala, Saeed, Varaghchi, Jamileh Rezazadeh, Najafi, Maryam, Deschner, Selina, Glaser, Dieter, Huttel, Wolfgang, Kruer, Michael C., Kamsteeg, Erik-Jan, Takiyama, Yoshihisa, Zuchner, Stephan, Baets, Jonathan, Synofzik, Matthis, Schuele, Rebecca, Horvath, Rita, Houlden, Henry, Bartesaghi, Luca, Lee, Hwei-Jen, Ampatzis, Konstantinos, Pierson, Tyler Mark, Senderek, Jan, Wiessner, Manuela, Maroofian, Reza, Ni, Meng-Yuan, Pedroni, Andrea, Muller, Juliane S., Stucka, Rolf, Beetz, Christian, Efthymiou, Stephanie, Santorelli, Filippo M., Alfares, Ahmed A., Zhu, Changlian, Meszarosova, Anna Uhrova, Alehabib, Elham, Bakhtiari, Somayeh, Janecke, Andreas R., Otero, Maria Gabriela, Chen, Jin Yun Helen, Peterson, James T., Strom, Tim M., De Jonghe, Peter, Deconinck, Tine, De Ridder, Willem, De Winter, Jonathan, Pasquariello, Rossella, Ricca, Ivana, Alfadhel, Majid, van de Warrenburg, Bart P., Portier, Ruben, Bergmann, Carsten, Firouzabadi, Saghar Ghasemi, Jin, Sheng Chih, Bilguvar, Kaya, Hamed, Sherifa, Abdelhameed, Mohammed, Haridy, Nourelhoda A., Maqbool, Shazia, Rahman, Fatima, Anwar, Najwa, Carmichael, Jenny, Pagnamenta, Alistair, Wood, Nick W., Mau-Them, Frederic Tran, Haack, Tobias, Di Rocco, Maja, Ceccherini, Isabella, Iacomino, Michele, Zara, Federico, Salpietro, Vincenzo, Scala, Marcello, Rusmini, Marta, Xu, Yiran, Wang, Yinghong, Suzuki, Yasuhiro, Koh, Kishin, Nan, Haitian, Ishiura, Hiroyuki, Tsuji, Shoji, Lambert, Laetitia, Schmitt, Emmanuelle, Lacaze, Elodie, Kupper, Hanna, Dredge, David, Skraban, Cara, Goldstein, Amy, Willis, Mary J. H., Grand, Katheryn, Graham, John M., Lewis, Richard A., Millan, Francisca, Duman, Ozgur, Dundar, Nihal, Uyanik, Gokhan, Schols, Ludger, Nurnberg, Peter, Nurnberg, Gudrun, Bordes, Andrea Catala, Seeman, Pavel, Kuchar, Martin, Darvish, Hossein, Rebelo, Adriana, Boucanova, Filipa, Medard, Jean-Jacques, Chrast, Roman, Auer-Grumbach, Michaela, Alkuraya, Fowzan S., Shamseldin, Hanan, Al Tala, Saeed, Varaghchi, Jamileh Rezazadeh, Najafi, Maryam, Deschner, Selina, Glaser, Dieter, Huttel, Wolfgang, Kruer, Michael C., Kamsteeg, Erik-Jan, Takiyama, Yoshihisa, Zuchner, Stephan, Baets, Jonathan, Synofzik, Matthis, Schuele, Rebecca, Horvath, Rita, Houlden, Henry, Bartesaghi, Luca, Lee, Hwei-Jen, Ampatzis, Konstantinos, Pierson, Tyler Mark, and Senderek, Jan
- Abstract
Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays.
- Published
- 2021
28. Human induced pluripotent stem cell models for CLN6
- Author
-
Pierson, Tyler Mark, primary, Kushwaha, Yogesh K., additional, Otero, Maria Gabriela, additional, Kenny, Phillip J., additional, Nonis, Fabian David, additional, and Kim, Jaemin, additional
- Published
- 2021
- Full Text
- View/download PDF
29. Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy
- Author
-
Genetica Klinische Genetica, Brain, Child Health, Hengel, Holger, Bosso-Lefèvre, Célia, Grady, George, Szenker-Ravi, Emmanuelle, Li, Hankun, Pierce, Sarah, Lebigot, Élise, Tan, Thong-Teck, Eio, Michelle Y, Narayanan, Gunaseelan, Utami, Kagistia Hana, Yau, Monica, Handal, Nader, Deigendesch, Werner, Keimer, Reinhard, Marzouqa, Hiyam M, Gunay-Aygun, Meral, Muriello, Michael J, Verhelst, Helene, Weckhuysen, Sarah, Mahida, Sonal, Naidu, Sakkubai, Thomas, Terrence G, Lim, Jiin Ying, Tan, Ee Shien, Haye, Damien, Willemsen, Michèl A A P, Oegema, Renske, Mitchell, Wendy G, Pierson, Tyler Mark, Andrews, Marisa V, Willing, Marcia C, Rodan, Lance H, Barakat, Tahsin Stefan, van Slegtenhorst, Marjon, Gavrilova, Ralitza H, Martinelli, Diego, Gilboa, Tal, Tamim, Abdullah M, Hashem, Mais O, AlSayed, Moeenaldeen D, Abdulrahim, Maha M, Al-Owain, Mohammed, Awaji, Ali, Mahmoud, Adel A H, Faqeih, Eissa A, Asmari, Ali Al, Algain, Sulwan M, Jad, Lamyaa A, Aldhalaan, Hesham M, Helbig, Ingo, Koolen, David A, Riess, Angelika, Kraegeloh-Mann, Ingeborg, Bauer, Peter, Gulsuner, Suleyman, Stamberger, Hannah, Ng, Alvin Yu Jin, Tang, Sha, Tohari, Sumanty, Keren, Boris, Schultz-Rogers, Laura E, Klee, Eric W, Barresi, Sabina, Tartaglia, Marco, Mor-Shaked, Hagar, Maddirevula, Sateesh, Begtrup, Amber, Telegrafi, Aida, Pfundt, Rolph, Schüle, Rebecca, Ciruna, Brian, Bonnard, Carine, Pouladi, Mahmoud A, Stewart, James C, Claridge-Chang, Adam, Lefeber, Dirk J, Alkuraya, Fowzan S, Mathuru, Ajay S, Venkatesh, Byrappa, Barycki, Joseph J, Simpson, Melanie A, Jamuar, Saumya S, Schöls, Ludger, Reversade, Bruno, Genetica Klinische Genetica, Brain, Child Health, Hengel, Holger, Bosso-Lefèvre, Célia, Grady, George, Szenker-Ravi, Emmanuelle, Li, Hankun, Pierce, Sarah, Lebigot, Élise, Tan, Thong-Teck, Eio, Michelle Y, Narayanan, Gunaseelan, Utami, Kagistia Hana, Yau, Monica, Handal, Nader, Deigendesch, Werner, Keimer, Reinhard, Marzouqa, Hiyam M, Gunay-Aygun, Meral, Muriello, Michael J, Verhelst, Helene, Weckhuysen, Sarah, Mahida, Sonal, Naidu, Sakkubai, Thomas, Terrence G, Lim, Jiin Ying, Tan, Ee Shien, Haye, Damien, Willemsen, Michèl A A P, Oegema, Renske, Mitchell, Wendy G, Pierson, Tyler Mark, Andrews, Marisa V, Willing, Marcia C, Rodan, Lance H, Barakat, Tahsin Stefan, van Slegtenhorst, Marjon, Gavrilova, Ralitza H, Martinelli, Diego, Gilboa, Tal, Tamim, Abdullah M, Hashem, Mais O, AlSayed, Moeenaldeen D, Abdulrahim, Maha M, Al-Owain, Mohammed, Awaji, Ali, Mahmoud, Adel A H, Faqeih, Eissa A, Asmari, Ali Al, Algain, Sulwan M, Jad, Lamyaa A, Aldhalaan, Hesham M, Helbig, Ingo, Koolen, David A, Riess, Angelika, Kraegeloh-Mann, Ingeborg, Bauer, Peter, Gulsuner, Suleyman, Stamberger, Hannah, Ng, Alvin Yu Jin, Tang, Sha, Tohari, Sumanty, Keren, Boris, Schultz-Rogers, Laura E, Klee, Eric W, Barresi, Sabina, Tartaglia, Marco, Mor-Shaked, Hagar, Maddirevula, Sateesh, Begtrup, Amber, Telegrafi, Aida, Pfundt, Rolph, Schüle, Rebecca, Ciruna, Brian, Bonnard, Carine, Pouladi, Mahmoud A, Stewart, James C, Claridge-Chang, Adam, Lefeber, Dirk J, Alkuraya, Fowzan S, Mathuru, Ajay S, Venkatesh, Byrappa, Barycki, Joseph J, Simpson, Melanie A, Jamuar, Saumya S, Schöls, Ludger, and Reversade, Bruno
- Published
- 2020
30. Correction: GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder
- Author
-
Shieh, Christine, Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden Y, Silva, Ana PG, Lee, Hane, Douine, Emilie D, Otero, Maria G, Choi, Andrew, Grand, Katheryn, Taff, Ingrid P, Delgado, Mauricio R, Hajianpour, MJ, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen W, Vergano, Samantha A, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana Berta, Wain, Karen E, Challman, Thomas D, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James J, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren DM, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane A, Hurst, Jane, Fitzpatrick, David R, Morton, Jenny EV, Cox, Helen, Venkateswaran, Sunita, Young, Juan I, Marsh, Eric D, Nelson, Stanley F, Martinez, Julian A, Graham, John M, Kini, Usha, Mackay, Joel P, Pierson, Tyler Mark, Shieh, Christine, Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden Y, Silva, Ana PG, Lee, Hane, Douine, Emilie D, Otero, Maria G, Choi, Andrew, Grand, Katheryn, Taff, Ingrid P, Delgado, Mauricio R, Hajianpour, MJ, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen W, Vergano, Samantha A, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana Berta, Wain, Karen E, Challman, Thomas D, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James J, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren DM, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane A, Hurst, Jane, Fitzpatrick, David R, Morton, Jenny EV, Cox, Helen, Venkateswaran, Sunita, Young, Juan I, Marsh, Eric D, Nelson, Stanley F, Martinez, Julian A, Graham, John M, Kini, Usha, Mackay, Joel P, and Pierson, Tyler Mark
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
31. Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2
- Author
-
Zarate, Yuri A., primary, Bosanko, Katherine A., additional, Thomas, Mary Ann, additional, Miller, David T., additional, Cusmano‐Ozog, Kristina, additional, Martinez‐Monseny, Antonio, additional, Curry, Cynthia J., additional, Graham, John M., additional, Velsher, Lea, additional, Bekheirnia, Mir Reza, additional, Seidel, Veronica, additional, Dedousis, Demitrios, additional, Mitchell, Anna L., additional, DiMarino, Amy M., additional, Riess, Angelika, additional, Balasubramanian, Meena, additional, Fish, Jennifer L., additional, Caffrey, Aisling R., additional, Fleischer, Nicole, additional, Pierson, Tyler Mark, additional, and Lacro, Ronald V., additional
- Published
- 2021
- Full Text
- View/download PDF
32. Auditory analysis of xeroderma pigmentosum 1971–2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration
- Author
-
Totonchy, Mariam B., Tamura, Deborah, Pantell, Matthew S., Zalewski, Christopher, Bradford, Porcia T., Merchant, Saumil N., Nadol, Joseph, Khan, Sikandar G., Schiffmann, Raphael, Pierson, Tyler Mark, Wiggs, Edythe, Griffith, Andrew J., DiGiovanna, John J., Kraemer, Kenneth H., and Brewer, Carmen C.
- Published
- 2013
- Full Text
- View/download PDF
33. GATAD2B-associatedneurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-relateddisorder
- Author
-
Shieh, Christine, primary, Jones, Natasha, additional, Vanle, Brigitte, additional, Au, Margaret, additional, Huang, Alden Y., additional, Silva, Ana P.G., additional, Lee, Hane, additional, Douine, Emilie D., additional, Otero, Maria G., additional, Choi, Andrew, additional, Grand, Katheryn, additional, Taff, Ingrid P., additional, Delgado, Mauricio R., additional, Hajianpour, M.J., additional, Seeley, Andrea, additional, Rohena, Luis, additional, Vernon, Hilary, additional, Gripp, Karen W., additional, Vergano, Samantha A., additional, Mahida, Sonal, additional, Naidu, Sakkubai, additional, Sousa, Ana Berta, additional, Wain, Karen E., additional, Challman, Thomas D., additional, Beek, Geoffrey, additional, Basel, Donald, additional, Ranells, Judith, additional, Smith, Rosemarie, additional, Yusupov, Roman, additional, Freckmann, Mary-Louise, additional, Ohden, Lisa, additional, Davis-Keppen, Laura, additional, Chitayat, David, additional, Dowling, James J., additional, Finkel, Richard, additional, Dauber, Andrew, additional, Spillmann, Rebecca, additional, Pena, Loren D.M., additional, Metcalfe, Kay, additional, Splitt, Miranda, additional, Lachlan, Katherine, additional, McKee, Shane A., additional, Hurst, Jane, additional, Fitzpatrick, David R., additional, Morton, Jenny E.V., additional, Cox, Helen, additional, Venkateswaran, Sunita, additional, Young, Juan I., additional, Marsh, Eric D., additional, Nelson, Stanley F., additional, Martinez, Julian A., additional, Graham, John M., additional, Kini, Usha, additional, Mackay, Joel P., additional, and Pierson, Tyler Mark, additional
- Published
- 2020
- Full Text
- View/download PDF
34. Correction: GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder
- Author
-
Shieh, Christine, primary, Jones, Natasha, additional, Vanle, Brigitte, additional, Au, Margaret, additional, Huang, Alden Y., additional, Silva, Ana P.G., additional, Lee, Hane, additional, Douine, Emilie D., additional, Otero, Maria G., additional, Choi, Andrew, additional, Grand, Katheryn, additional, Taff, Ingrid P., additional, Delgado, Mauricio R., additional, Hajianpour, M.J., additional, Seeley, Andrea, additional, Rohena, Luis, additional, Vernon, Hilary, additional, Gripp, Karen W., additional, Vergano, Samantha A., additional, Mahida, Sonal, additional, Naidu, Sakkubai, additional, Sousa, Ana Berta, additional, Wain, Karen E., additional, Challman, Thomas D., additional, Beek, Geoffrey, additional, Basel, Donald, additional, Ranells, Judith, additional, Smith, Rosemarie, additional, Yusupov, Roman, additional, Freckmann, Mary-Louise, additional, Ohden, Lisa, additional, Davis-Keppen, Laura, additional, Chitayat, David, additional, Dowling, James J., additional, Finkel, Richard, additional, Dauber, Andrew, additional, Spillmann, Rebecca, additional, Pena, Loren D.M., additional, Metcalfe, Kay, additional, Splitt, Miranda, additional, Lachlan, Katherine, additional, McKee, Shane A., additional, Hurst, Jane, additional, Fitzpatrick, David R., additional, Morton, Jenny E.V., additional, Cox, Helen, additional, Venkateswaran, Sunita, additional, Young, Juan I., additional, Marsh, Eric D., additional, Nelson, Stanley F., additional, Martinez, Julian A., additional, Graham, John M., additional, Kini, Usha, additional, Mackay, Joel P., additional, and Pierson, Tyler Mark, additional
- Published
- 2020
- Full Text
- View/download PDF
35. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling
- Author
-
Johnson, Brett V., primary, Kumar, Raman, additional, Oishi, Sabrina, additional, Alexander, Suzy, additional, Kasherman, Maria, additional, Vega, Michelle Sanchez, additional, Ivancevic, Atma, additional, Gardner, Alison, additional, Domingo, Deepti, additional, Corbett, Mark, additional, Parnell, Euan, additional, Yoon, Sehyoun, additional, Oh, Tracey, additional, Lines, Matthew, additional, Lefroy, Henrietta, additional, Kini, Usha, additional, Van Allen, Margot, additional, Grønborg, Sabine, additional, Mercier, Sandra, additional, Küry, Sébastien, additional, Bézieau, Stéphane, additional, Pasquier, Laurent, additional, Raynaud, Martine, additional, Afenjar, Alexandra, additional, Billette de Villemeur, Thierry, additional, Keren, Boris, additional, Désir, Julie, additional, Van Maldergem, Lionel, additional, Marangoni, Martina, additional, Dikow, Nicola, additional, Koolen, David A., additional, VanHasselt, Peter M., additional, Weiss, Marjan, additional, Zwijnenburg, Petra, additional, Sa, Joaquim, additional, Reis, Claudia Falcao, additional, López-Otín, Carlos, additional, Santiago-Fernández, Olaya, additional, Fernández-Jaén, Alberto, additional, Rauch, Anita, additional, Steindl, Katharina, additional, Joset, Pascal, additional, Goldstein, Amy, additional, Madan-Khetarpal, Suneeta, additional, Infante, Elena, additional, Zackai, Elaine, additional, Mcdougall, Carey, additional, Narayanan, Vinodh, additional, Ramsey, Keri, additional, Mercimek-Andrews, Saadet, additional, Pena, Loren, additional, Shashi, Vandana, additional, Schoch, Kelly, additional, Sullivan, Jennifer A., additional, Pinto e Vairo, Filippo, additional, Pichurin, Pavel N., additional, Ewing, Sarah A., additional, Barnett, Sarah S., additional, Klee, Eric W., additional, Perry, M. Scott, additional, Koenig, Mary Kay, additional, Keegan, Catherine E., additional, Schuette, Jane L., additional, Asher, Stephanie, additional, Perilla-Young, Yezmin, additional, Smith, Laurie D., additional, Rosenfeld, Jill A., additional, Bhoj, Elizabeth, additional, Kaplan, Paige, additional, Li, Dong, additional, Oegema, Renske, additional, van Binsbergen, Ellen, additional, van der Zwaag, Bert, additional, Smeland, Marie Falkenberg, additional, Cutcutache, Ioana, additional, Page, Matthew, additional, Armstrong, Martin, additional, Lin, Angela E., additional, Steeves, Marcie A., additional, Hollander, Nicolette den, additional, Hoffer, Mariëtte J.V., additional, Reijnders, Margot R.F., additional, Demirdas, Serwet, additional, Koboldt, Daniel C., additional, Bartholomew, Dennis, additional, Mosher, Theresa Mihalic, additional, Hickey, Scott E., additional, Shieh, Christine, additional, Sanchez-Lara, Pedro A., additional, Graham, John M., additional, Tezcan, Kamer, additional, Schaefer, G.B., additional, Danylchuk, Noelle R., additional, Asamoah, Alexander, additional, Jackson, Kelly E., additional, Yachelevich, Naomi, additional, Au, Margaret, additional, Pérez-Jurado, Luis A., additional, Kleefstra, Tjitske, additional, Penzes, Peter, additional, Wood, Stephen A., additional, Burne, Thomas, additional, Pierson, Tyler Mark, additional, Piper, Michael, additional, Gécz, Jozef, additional, Jolly, Lachlan A., additional, Acosta, Maria T., additional, Adams, David R., additional, Aday, Aaron, additional, Alejandro, Mercedes E., additional, Allard, Patrick, additional, Ashley, Euan A., additional, Azamian, Mahshid S., additional, Bacino, Carlos A., additional, Bademci, Guney, additional, Baker, Eva, additional, Balasubramanyam, Ashok, additional, Baldridge, Dustin, additional, Barbouth, Deborah, additional, Batzli, Gabriel F., additional, Beggs, Alan H., additional, Bellen, Hugo J., additional, Bernstein, Jonathan A., additional, Berry, Gerard T., additional, Bican, Anna, additional, Bick, David P., additional, Birch, Camille L., additional, Bivona, Stephanie, additional, Bonnenmann, Carsten, additional, Bonner, Devon, additional, Boone, Braden E., additional, Bostwick, Bret L., additional, Briere, Lauren C., additional, Brokamp, Elly, additional, Brown, Donna M., additional, Brush, Matthew, additional, Burke, Elizabeth A., additional, Burrage, Lindsay C., additional, Butte, Manish J., additional, Carrasquillo, Olveen, additional, Peter Chang, Ta Chen, additional, Chao, Hsiao-Tuan, additional, Clark, Gary D., additional, Coakley, Terra R., additional, Cobban, Laurel A., additional, Cogan, Joy D., additional, Cole, F. Sessions, additional, Colley, Heather A., additional, Cooper, Cynthia M., additional, Cope, Heidi, additional, Craigen, William J., additional, D'Souza, Precilla, additional, Dasari, Surendra, additional, Davids, Mariska, additional, Davidson, Jean M., additional, Dayal, Jyoti G., additional, Dell'Angelica, Esteban C., additional, Dhar, Shweta U., additional, Dorrani, Naghmeh, additional, Dorset, Daniel C., additional, Douine, Emilie D., additional, Draper, David D., additional, Dries, Annika M., additional, Duncan, Laura, additional, Eckstein, David J., additional, Emrick, Lisa T., additional, Eng, Christine M., additional, Enns, Gregory M., additional, Esteves, Cecilia, additional, Estwick, Tyra, additional, Fernandez, Liliana, additional, Ferreira, Carlos, additional, Fieg, Elizabeth L., additional, Fisher, Paul G., additional, Fogel, Brent L., additional, Forghani, Irman, additional, Friedman, Noah D., additional, Gahl, William A., additional, Godfrey, Rena A., additional, Goldman, Alica M., additional, Goldstein, David B., additional, Gourdine, Jean-Philippe F., additional, Grajewski, Alana, additional, Groden, Catherine A., additional, Gropman, Andrea L., additional, Haendel, Melissa, additional, Hamid, Rizwan, additional, Hanchard, Neil A., additional, High, Frances, additional, Holm, Ingrid A., additional, Hom, Jason, additional, Huang, Alden, additional, Huang, Yong, additional, Isasi, Rosario, additional, Jamal, Fariha, additional, Jiang, Yong-hui, additional, Johnston, Jean M., additional, Jones, Angela L., additional, Karaviti, Lefkothea, additional, Kelley, Emily G., additional, Koeller, David M., additional, Kohane, Isaac S., additional, Kohler, Jennefer N., additional, Krakow, Deborah, additional, Krasnewich, Donna M., additional, Korrick, Susan, additional, Koziura, Mary, additional, Krier, Joel B., additional, Kyle, Jennifer E., additional, Lalani, Seema R., additional, Lam, Byron, additional, Lanpher, Brendan C., additional, Lanza, Ian R., additional, Lau, C. Christopher, additional, Lazar, Jozef, additional, LeBlanc, Kimberly, additional, Lee, Brendan H., additional, Lee, Hane, additional, Levitt, Roy, additional, Levy, Shawn E., additional, Lewis, Richard A., additional, Lincoln, Sharyn A., additional, Liu, Pengfei, additional, Liu, Xue Zhong, additional, Loo, Sandra K., additional, Loscalzo, Joseph, additional, Maas, Richard L., additional, Macnamara, Ellen F., additional, MacRae, Calum A., additional, Maduro, Valerie V., additional, Majcherska, Marta M., additional, Malicdan, May Christine V., additional, Mamounas, Laura A., additional, Manolio, Teri A., additional, Markello, Thomas C., additional, Marom, Ronit, additional, Martin, Martin G., additional, Martínez-Agosto, Julian A., additional, Marwaha, Shruti, additional, May, Thomas, additional, McCauley, Jacob, additional, McConkie-Rosell, Allyn, additional, McCormack, Colleen E., additional, McCray, Alexa T., additional, Merker, Jason D., additional, Metz, Thomas O., additional, Might, Matthew, additional, Morava-Kozicz, Eva, additional, Moretti, Paolo M., additional, Morimoto, Marie, additional, Mulvihill, John J., additional, Murdock, David R., additional, Nath, Avi, additional, Nelson, Stan F., additional, Newberry, J. Scott, additional, Newman, John H., additional, Nicholas, Sarah K., additional, Novacic, Donna, additional, Oglesbee, Devin, additional, Orengo, James P., additional, Pak, Stephen, additional, Pallais, J. Carl, additional, Palmer, Christina GS., additional, Papp, Jeanette C., additional, Parker, Neil H., additional, Phillips, John A., additional, Posey, Jennifer E., additional, Postlethwait, John H., additional, Potocki, Lorraine, additional, Pusey, Barbara N., additional, Renteri, Genecee, additional, Reuter, Chloe M., additional, Rives, Lynette, additional, Robertson, Amy K., additional, Rodan, Lance H., additional, Rowley, Robb K., additional, Sacco, Ralph, additional, Sampson, Jacinda B., additional, Samson, Susan L., additional, Saporta, Mario, additional, Schaechter, Judy, additional, Schedl, Timothy, additional, Scott, Daryl A., additional, Shakachite, Lisa, additional, Sharma, Prashant, additional, Shields, Kathleen, additional, Shin, Jimann, additional, Signer, Rebecca, additional, Sillari, Catherine H., additional, Silverman, Edwin K., additional, Sinsheimer, Janet S., additional, Smith, Kevin S., additional, Solnica-Krezel, Lilianna, additional, Spillmann, Rebecca C., additional, Stoler, Joan M., additional, Stong, Nicholas, additional, Sweetser, David A., additional, Tamburro, Cecelia P., additional, Tan, Queenie K.-G., additional, Tekin, Mustafa, additional, Telischi, Fred, additional, Thorson, Willa, additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Tran, Alyssa A., additional, Urv, Tiina K., additional, Vogel, Tiphanie P., additional, Waggott, Daryl M., additional, Wahl, Colleen E., additional, Walley, Nicole M., additional, Walsh, Chris A., additional, Walker, Melissa, additional, Wambach, Jennifer, additional, Wan, Jijun, additional, Wang, Lee-kai, additional, Wangler, Michael F., additional, Ward, Patricia A., additional, Waters, Katrina M., additional, Webb-Robertson, Bobbie-Jo M., additional, Wegner, Daniel, additional, Westerfield, Monte, additional, Wheeler, Matthew T., additional, Wise, Anastasia L., additional, Wolfe, Lynne A., additional, Woods, Jeremy D., additional, Worthey, Elizabeth A., additional, Yamamoto, Shinya, additional, Yang, John, additional, Yoon, Amanda J., additional, Yu, Guoyun, additional, Zastrow, Diane B., additional, Zhao, Chunli, additional, Zuchner, Stephan, additional, and Gahl, William, additional
- Published
- 2020
- Full Text
- View/download PDF
36. The NuRD complex and macrocephaly associated neurodevelopmental disorders
- Author
-
Pierson, Tyler Mark, primary, Otero, Maria G., additional, Grand, Katheryn, additional, Choi, Andrew, additional, Graham, John M., additional, Young, Juan I., additional, and Mackay, Joel P., additional
- Published
- 2019
- Full Text
- View/download PDF
37. Regulable Expression of Inhibin A in Wild-Type and Inhibin α Null Mice
- Author
-
Pierson, Tyler Mark, Wang, Yaolin, DeMayo, Francesco J, Matzuk, Martin M, Tsai, Sophia Y, and O’Malley, Bert W
- Published
- 2000
38. Modeling CLN6 with IPSC-derived neural cells
- Author
-
Pierson, Tyler Mark, primary, Otero, Maria Gabriella, additional, Nonis, David Fabian, additional, and Kim, Jaemin, additional
- Published
- 2019
- Full Text
- View/download PDF
39. Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy
- Author
-
Otero, Maria G., primary, Tiongson, Emmanuelle, additional, Diaz, Frank, additional, Haude, Katrina, additional, Panzer, Karin, additional, Collier, Ashley, additional, Kim, Jaemin, additional, Adams, David, additional, Tifft, Cynthia J., additional, Cui, Hong, additional, Millian Zamora, Francisca, additional, Au, Margaret G., additional, Graham, John M., additional, Buckley, David J., additional, Lewis, Richard, additional, Toro, Camilo, additional, Bai, Renkui, additional, Turner, Lesley, additional, Mathews, Katherine D., additional, Gahl, William, additional, and Pierson, Tyler Mark, additional
- Published
- 2018
- Full Text
- View/download PDF
40. Acid ceramidase deficiency associated with spinal muscular atrophy with progressive myoclonic epilepsy
- Author
-
Gan, Joanna J., Garcia, Virginie, Tian, Jane, Tagliati, Michele, Parisi, Joseph E., Chung, Jeffrey M., Lewis, Richard, Baloh, Robert, Levade, Thierry, and Pierson, Tyler Mark
- Published
- 2015
- Full Text
- View/download PDF
41. Modeling CLN6 with patient-derived IPS cells
- Author
-
Pierson, Tyler Mark, primary
- Published
- 2017
- Full Text
- View/download PDF
42. Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy
- Author
-
Schartner, Vanessa, primary, Romero, Norma B., additional, Donkervoort, Sandra, additional, Treves, Susan, additional, Munot, Pinki, additional, Pierson, Tyler Mark, additional, Dabaj, Ivana, additional, Malfatti, Edoardo, additional, Zaharieva, Irina T., additional, Zorzato, Francesco, additional, Abath Neto, Osorio, additional, Brochier, Guy, additional, Lornage, Xavière, additional, Eymard, Bruno, additional, Taratuto, Ana Lía, additional, Böhm, Johann, additional, Gonorazky, Hernan, additional, Ramos-Platt, Leigh, additional, Feng, Lucy, additional, Phadke, Rahul, additional, Bharucha-Goebel, Diana X., additional, Sumner, Charlotte Jane, additional, Bui, Mai Thao, additional, Lacene, Emmanuelle, additional, Beuvin, Maud, additional, Labasse, Clémence, additional, Dondaine, Nicolas, additional, Schneider, Raphael, additional, Thompson, Julie, additional, Boland, Anne, additional, Deleuze, Jean-François, additional, Matthews, Emma, additional, Pakleza, Aleksandra Nadaj, additional, Sewry, Caroline A., additional, Biancalana, Valérie, additional, Quijano-Roy, Susana, additional, Muntoni, Francesco, additional, Fardeau, Michel, additional, Bönnemann, Carsten G., additional, and Laporte, Jocelyn, additional
- Published
- 2016
- Full Text
- View/download PDF
43. Mutation in the sixth immunoglobulin domain ofL1CAMis associated with migrational brain anomalies
- Author
-
Shieh, Christine, primary, Moser, Franklin, additional, Graham, John M., additional, Watiker, Valerie, additional, and Pierson, Tyler Mark, additional
- Published
- 2015
- Full Text
- View/download PDF
44. De novo and biallelic DEAF1variants cause a phenotypic spectrum
- Author
-
Nabais Sá, Maria J., Jensik, Philip J., McGee, Stacey R., Parker, Michael J., Lahiri, Nayana, McNeil, Evan P., Kroes, Hester Y., Hagerman, Randi J., Harrison, Rachel E., Montgomery, Tara, Splitt, Miranda, Palmer, Elizabeth E., Sachdev, Rani K., Mefford, Heather C., Scott, Abbey A., Martinez-Agosto, Julian A., Lorenz, Rüdiger, Orenstein, Naama, Berg, Jonathan N., Amiel, Jeanne, Heron, Delphine, Keren, Boris, Cobben, Jan-Maarten, Menke, Leonie A., Marco, Elysa J., Graham, John M., Pierson, Tyler Mark, Karimiani, Ehsan Ghayoor, Maroofian, Reza, Manzini, M. Chiara, Cauley, Edmund S., Colombo, Roberto, Odent, Sylvie, Dubourg, Christele, Phornphutkul, Chanika, de Brouwer, Arjan P.M., de Vries, Bert B.A., and Vulto-vanSilfhout, Anneke T.
- Abstract
To investigate the effect of different DEAF1variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and on DEAF1 activity in vitro.
- Published
- 2019
- Full Text
- View/download PDF
45. Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy.
- Author
-
Yuan, Hongjie, Yuan, Hongjie, Hansen, Kasper B, Zhang, Jing, Pierson, Tyler Mark, Markello, Thomas C, Fajardo, Karin V Fuentes, Holloman, Conisha M, Golas, Gretchen, Adams, David R, Boerkoel, Cornelius F, Gahl, William A, Traynelis, Stephen F, Yuan, Hongjie, Yuan, Hongjie, Hansen, Kasper B, Zhang, Jing, Pierson, Tyler Mark, Markello, Thomas C, Fajardo, Karin V Fuentes, Holloman, Conisha M, Golas, Gretchen, Adams, David R, Boerkoel, Cornelius F, Gahl, William A, and Traynelis, Stephen F
- Abstract
NMDA receptors (NMDARs), ligand-gated ion channels, play important roles in various neurological disorders, including epilepsy. Here we show the functional analysis of a de novo missense mutation (L812M) in a gene encoding NMDAR subunit GluN2A (GRIN2A). The mutation, identified in a patient with early-onset epileptic encephalopathy and profound developmental delay, is located in the linker region between the ligand-binding and transmembrane domains. Electrophysiological recordings revealed that the mutation enhances agonist potency, decreases sensitivity to negative modulators including magnesium, protons and zinc, prolongs the synaptic response time course and increases single-channel open probability. The functional changes of this amino acid apply to all other NMDAR subunits, suggesting an important role of this residue on the function of NMDARs. Taken together, these data suggest that the L812M mutation causes overactivation of NMDARs and drives neuronal hyperexcitability. We hypothesize that this mechanism underlies the patient's epileptic phenotype as well as cerebral atrophy.
- Published
- 2014
46. Infantile-onset spinal muscular atrophy with respiratory distress-1 diagnosed in a 20-year-old man
- Author
-
Pierson, Tyler Mark, Tart, Gary, Adams, David, Toro, Camilo, Golas, Gretchen, Tifft, Cynthia, and Gahl, William
- Published
- 2011
- Full Text
- View/download PDF
47. Lysosomal abnormalities in hereditary spastic paraplegia types SPG 15 and SPG 11
- Author
-
Renvoisé, Benoît, primary, Chang, Jaerak, additional, Singh, Rajat, additional, Yonekawa, Sayuri, additional, FitzGibbon, Edmond J., additional, Mankodi, Ami, additional, Vanderver, Adeline, additional, Schindler, Alice B., additional, Toro, Camilo, additional, Gahl, William A., additional, Mahuran, Don J., additional, Blackstone, Craig, additional, and Pierson, Tyler Mark, additional
- Published
- 2014
- Full Text
- View/download PDF
48. Hereditary spastic paraplegias types 15 and 11 are associated with lysosomal abnormalities
- Author
-
Pierson, Tyler Mark, primary, Renvoisé, Benoît, additional, Chang, Jaerak, additional, Toro, Camilo, additional, and Blackstone, Craig, additional
- Published
- 2014
- Full Text
- View/download PDF
49. Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases
- Author
-
Pierson, Tyler Mark, Adams, David, Bonn, Florian, Martinelli, Paola, Cherukuri, Praveen F., Teer, Jamie K., Hansen, Nancy F., Cruz, Pedro, Mullikin, James C., Blakesley, Robert W., Golas, Gretchen, Kwan, Justin, Sandler, Anthony, Fajardo, Karin Fuentes, Markello, Thomas, Tifft, Cynthia, Blackstone, Craig, Rugarli, Elena I., Langer, Thomas, Gahl, William A., Toro, Camilo, Pierson, Tyler Mark, Adams, David, Bonn, Florian, Martinelli, Paola, Cherukuri, Praveen F., Teer, Jamie K., Hansen, Nancy F., Cruz, Pedro, Mullikin, James C., Blakesley, Robert W., Golas, Gretchen, Kwan, Justin, Sandler, Anthony, Fajardo, Karin Fuentes, Markello, Thomas, Tifft, Cynthia, Blackstone, Craig, Rugarli, Elena I., Langer, Thomas, Gahl, William A., and Toro, Camilo
- Abstract
We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other mitochondrial'' features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.
- Published
- 2011
50. Correction: Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases
- Author
-
Pierson, Tyler Mark, primary, Adams, David, additional, Bonn, Florian, additional, Martinelli, Paola, additional, Cherukuri, Praveen F., additional, Teer, Jamie K., additional, Hansen, Nancy F., additional, Cruz, Pedro, additional, Mullikin, James C., additional, Blakesley, Robert W., additional, Golas, Gretchen, additional, Kwan, Justin, additional, Sandler, Anthony, additional, Fuentes Fajardo, Karin, additional, Markello, Thomas, additional, Tifft, Cynthia, additional, Blackstone, Craig, additional, Rugarli, Elena I., additional, Langer, Thomas, additional, Gahl, William A., additional, and Toro, Camilo, additional
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.