No association between SCN9A and monogenic human epilepsy disorders.

James Fasham, Joseph S Leslie, Jamie W Harrison, James Deline, Katie B Williams, Ashley Kuhl, Jessica Scott Schwoerer, Harold E Cross, Andrew H Crosby, Emma L Baple

PLoS genetics 2020 Nov

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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.

Citation

James Fasham, Joseph S Leslie, Jamie W Harrison, James Deline, Katie B Williams, Ashley Kuhl, Jessica Scott Schwoerer, Harold E Cross, Andrew H Crosby, Emma L Baple. No association between SCN9A and monogenic human epilepsy disorders. PLoS genetics. 2020 Nov;16(11):e1009161