No association between SCN9A and monogenic human epilepsy disorders

English version

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: https://doi.org/10.1371/journal.pgen.1009161

Souhrn

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

Zdroje

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