Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load

P Perucca; A Anderson; D Jazayeri; A Hitchcock; J Graham; M Todaro; T Tomson; D Battino; E Perucca; MM Ferri; A Rochtus; L Lagae; MP Canevini; E Zambrelli; E Campbell; BPC Koeleman; IE Scheffer; SF Berkovic; P Kwan; SM Sisodiya; DB Goldstein; S Petrovski; J Craig; FJE Vajda; TJ O'Brien

Journal article

Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load

P Perucca, A Anderson, D Jazayeri, A Hitchcock, J Graham, M Todaro, T Tomson, D Battino, E Perucca, MM Ferri, A Rochtus, L Lagae, MP Canevini, E Zambrelli, E Campbell, BPC Koeleman, IE Scheffer, SF Berkovic, P Kwan, SM Sisodiya Show all

Annals of Neurology | WILEY | Published : 2020

DOI: 10.1002/ana.25724

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Abstract

Objective: The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, a mechanism that we investigated. Methods: Whole exome sequencing data from child–parent trios were interrogated for de novo single-nucleotide variants/indels (dnSNVs/indels) and de novo copy number variants (dnCNVs). Generalized linear models were applied to assess de novo variant burdens in children exposed prenatally to AEDs (AED-exposed children) versus children without BDs not exposed prenatally to AEDs (AED-unexposed unaffected children), and AED-exposed children with BDs versus t..

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University of Melbourne Researchers

Piero Perucca Author

Alison Anderson Author

Marian Todaro Author

Emilio Perucca Author

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Grants

Awarded by Sylvia and Charles Viertel Charitable Foundation

Funding Acknowledgements

The study was funded by a National Health and Medical Research Council (NHMRC) Project Grant (APP1059858) to T.J.O., S.P., D.B.G., F.J.E.V., P.K., J.C., S.F.B., and I.E.S.; an NHMRC Program Grant (APP1091593) to T.J.O., S.F.B., and I.E.S.; and the European Commission grant 279062, EpiPGX (to EpiPGX consortium, B.P.C.K., J.C., and S.M.S.). P.P. is supported by an NHMRC Early Career Fellowship (APP1163708) and by the Viertel Clinical Investigator Award from the Sylvia and Charles Viertel Charitable Foundation. A.R. is funded by internal funds of the University of Leuven (PDM/17/195).