Journal article

Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load

Piero Perucca, Alison Anderson, Dana Jazayeri, Alison Hitchcock, Janet Graham, Marian Todaro, Torbjorn Tomson, Dina Battino, Emilio Perucca, Meritxell Martinez Ferri, Anne Rochtus, Lieven Lagae, Maria Paola Canevini, Elena Zambrelli, Ellen Campbell, Bobby PC Koeleman, Ingrid E Scheffer, Samuel F Berkovic, Patrick Kwan, Sanjay M Sisodiya Show all

ANNALS OF NEUROLOGY | WILEY | Published : 2020


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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Awarded by National Health and Medical Research Council (NHMRC)

Awarded by European Commission

Awarded by University of Leuven

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).