Open AccessNo association between SCN9A and monogenic human epilepsy disorders
Author(s) -
James Fasham,
Joseph S Leslie,
James W. Harrison,
James Deline,
Katie B. Williams,
Ashley Kuhl,
Jessica Scott Schwoerer,
Harold E. Cross,
Andrew H. Crosby,
Emma L. Baple
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009161
Subject(s) - biobank , epilepsy , biology , phenotype , disease , etiology , genetic association , clinical phenotype , epilepsy syndromes , candidate gene , bioinformatics , genetic testing , seizure disorders , genetics , gene , medicine , neuroscience , single nucleotide polymorphism , genotype
Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile seizures plus and other monogenic seizure phenotypes indistinguishable from those associated with SCN1A , leading to inclusion of SCN9A on epilepsy gene testing panels. Here we present serendipitous findings of genetic studies that identify the SCN9A c.1921A>T p.(Asn641Tyr) variant at high frequency in the Amish community in the absence of such seizure phenotypes. Together with findings in UK Biobank these data refute an association of SCN9A with epilepsy, which has important clinical diagnostic implications.