No association between SCN9A and monogenic human epilepsy disorders. PLoS Genet 2020 Nov;16(11):e1009161
Date
11/21/2020Pubmed ID
33216760Pubmed Central ID
PMC7717534DOI
10.1371/journal.pgen.1009161Scopus ID
2-s2.0-85097156765 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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.
Author List
Fasham J, Leslie JS, Harrison JW, Deline J, Williams KB, Kuhl A, Scott Schwoerer J, Cross HE, Crosby AH, Baple ELAuthor
Jessica Scott Schwoerer MD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionAmish
Child
Child, Preschool
Diagnostic Errors
Epilepsy
Female
Follow-Up Studies
Gene Frequency
Genetic Predisposition to Disease
Genetic Testing
Heterozygote
Humans
Infant
Male
Mutation
NAV1.7 Voltage-Gated Sodium Channel
Pedigree
Polymorphism, Single Nucleotide
Wisconsin
