a role of scn9a in human epilepsies, as a cause of febrile seizures and as a potential modifier of dravet syndromescn9a的作用在人类的癫痫病,发热性癫痫发作的一个原因,作为一个潜在的dravet综合症的修饰符.pdfVIP

A Role of SCN9A in Human Epilepsies, As a Cause of Febrile Seizures and As a Potential Modifier of Dravet Syndrome 1 1 1 2 3 2 Nanda A. Singh *, Chris Pappas , E. Jill Dahle , Lieve R. F. Claes , Timothy H. Pruess , Peter De Jonghe , 4 1 5 6 3 4 Joel Thompson , Missy Dixon , Christina Gurnett , Andy Peiffer , H. Steve White , Francis Filloux , Mark F. Leppert1 1 Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America, 2 VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium, 3 Department of Pharmacology and Toxicology, Anticonvulsant Drug Development Program, University of Utah, Salt Lake City, Utah, United States of America, 4 Division of Pediatric Neurology, University of Utah, Salt Lake City, Utah, United States of America, 5 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 6 Division of Medical Genetics, University of Utah, Salt Lake City, Utah, United States of America Abstract A follow-up study of a large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Nav 1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains I and II that was absent from 586 ethnically matched population control chromosomes. To establish a functional role for this mutation in seizure susceptibility, we introduced the orthologous mutation into the murine Scn9a ortholog using targeted