Journal article

Diverse genetic causes of polymicrogyria with epilepsy

Andrew S Allen, Vimla Aggarwal, Samuel F Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan E Eichler, Michael P Epstein, Catharine Freyer, David B Goldstein, Renzo Guerrini, Tracy Glauser, Erin L Heinzen, Michael R Johnson, Ruben Kuzniecky, Daniel H Lowenstein, Anthony G Marson, Heather C Mefford, Terence J O'Brien, Ruth Ottman Show all

EPILEPSIA | WILEY | Published : 2021

Abstract

OBJECTIVE: We sought to identify novel genes and to establish the contribution of known genes in a large cohort of patients with nonsyndromic sporadic polymicrogyria and epilepsy. METHODS: We enrolled participants with polymicrogyria and their parents through the Epilepsy Phenome/Genome Project. We performed phenotyping and whole exome sequencing (WES), trio analysis, and gene-level collapsing analysis to identify de novo or inherited variants, including germline or mosaic (postzygotic) single nucleotide variants, small insertion-deletion (indel) variants, and copy number variants present in leukocyte-derived DNA. RESULTS: Across the cohort of 86 individuals with polymicrogyria and epilepsy,..

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Grants

Awarded by National Institute of Neurological Disorders and Stroke


Awarded by Bryan Alzheimer's Disease Research Center, National Institute on Aging


Awarded by B57 SAIC-Fredrick


Awarded by National Human Genome Research Institute (Yale Mendelian Genomics Center)


Awarded by National Institute of Mental Health


Awarded by National Institute of Diabetes and Digestive and Kidney Diseases


Awarded by National Institute of Allergy and Infectious Diseases (Division of Intramural Research)


Awarded by National Center for Advancing Translational Sciences


Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development


Awarded by Ellison Medical Foundation New Scholar Award


Awarded by WHICAP - National Institute on Aging


Awarded by National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery


Awarded by National Center for Advancing Translational Sciences, National Institutes of Health


Funding Acknowledgements

We thank the patients and families who enrolled in the Epilepsy Phenotype/Genotype Project as well as the Community Referral Network of physicians who referred patients to the study. This study was supported by the National Institute of Neurological Disorders and Stroke (Epilepsy Phenome/Genome Project NS053998; Epi4K-Administrative Core NS077274; Epi4K-Sequencing, Biostatistics, and Bioinformatics Core NS077303; Epi4K-Project 1-Epileptic Encephalopathies NS077364, Epi4K-Phenotyping and Clinical Informatics Core NS077276).The collection of control samples and data was funded in part by Biogen; Gilead Sciences; UCB; Bryan Alzheimer's Disease Research Center, National Institute on Aging (P30AG028377); B57 SAIC-Fredrick (M11-074); National Institute of Neurological Disorders and Stroke (RC2NS070344, RC2MH089915, U01NS077303, U01NS053998, U54NS078059, P01HD080642); National Human Genome Research Institute (Yale Mendelian Genomics Center, UM1HG006504, U01HG007672); National Institute of Mental Health (K01MH098126, R01MH097971, R01MH099216, RC2MH089915); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080099); National Institute of Allergy and Infectious Diseases (Division of Intramural Research, 1R56AI098588-01A1); National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (UM1AI100645, U19AI067854); National Center for Advancing Translational Sciences (UL1TR000040); Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD048805); Ellison Medical Foundation New Scholar Award (AG-NS-0441-08); Duke Chancellor's Discovery Program Research Fund 2014; Neil Molberger Brain Research Fund; Endocrine Fellows Foundation Grant; Bill and Melinda Gates Foundation; Murdock Study Community Registry and Biorepository; Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratory; Duke Genome Sequencing Clinic; New York-Presbyterian Hospital; Columbia University College Physicians and Surgeons; Columbia University Medical Center; J. Willard and Alice S. Marriott Foundation; Muscular Dystrophy Association; Nicholas Nunno Foundation; JDM Fund for Mitochondrial Research; Arturo Estopinan TK2 Research Fund; Endocrine Fellows Foundation; and Helaine B. Allen and Emily Allen Wolff.Data collection and sharing with the Washington Heights-Inwood Columbia Aging Project (WHICAP; used for controls in this analysis) was supported by WHICAP (PO1AG07232, R01AG037212, RF1AG054023), funded by the National Institute on Aging and National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR001873. The manuscript was reviewed by WHICAP investigators for scientific content and consistency of data interpretation with previous WHICAP study publications. We acknowledge the WHICAP study participants and the WHICAP research and support staff for their contributions to this study.