No association between SCN9A and monogenic human epilepsy disorders

Autoři: James Fasham aff001;  Joseph S. Leslie aff001;  Jamie W. Harrison aff001;  James Deline aff004;  Katie B. Williams aff005;  Ashley Kuhl aff005;  Jessica Scott Schwoerer aff005;  Harold E. Cross aff006;  Andrew H. Crosby aff001;  Emma L. Baple aff001
Působiště autorů: RILD Wellcome Wolfson Centre, University of Exeter Medical School, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, United Kingdom aff001;  Peninsula Clinical Genetics Service, Royal Devon & Exeter Hospital, Gladstone Road, Exeter, United Kingdom aff002;  University of Exeter, Department of Biosciences, Exeter, United Kingdom aff003;  Center for Special Children, La Farge Medical Clinic-VMH, La Farge, Wisconsin, United States of America aff004;  Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States of America aff005;  Department of Ophthalmology, University of Arizona College of Medicine, Tucson, Arizona, United States of America aff006
Vyšlo v časopise: No association between SCN9A and monogenic human epilepsy disorders. PLoS Genet 16(11): e1009161. doi:10.1371/journal.pgen.1009161
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009161


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.

Klíčová slova:

Alleles – Clinical genetics – Epilepsy – Genetics – Genomics – Heterozygosity – Human genetics – Protein domains


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PLOS Genetics

2020 Číslo 11
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