title: A novel SCN1A missense mutation causes generalized epilepsy with febrile seizures plus in a Chinese family.
abstract: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a common familial epilepsy syndrome, which generally develops in childhood. GEFS(+) is caused by mutations in the sodium-channel α1-subunit (SCN1A). In this report, we investigated a Chinese family with an autosomal dominant form of GEFS(+). The affected GEFS(+) patients in this family displayed significant inter-family clinical heterogeneity. Linkage analysis localized the disease-causing gene to chromosome 2q24, where SCN1A is located. Furthermore, DNA sequencing of the whole coding region of SCN1A revealed a novel heterozygous nucleotide substitution (c.577C>T) causing a missense mutation (p.L193F) in the S3 segment of SCN1A domain D1. Our results expand the spectrum of SCN1A mutations and provide novel insights between the SCN1A mutations and the clinical variations of GEFS(+).
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Cui
authors.forename: Feng
authors.initials: F
authors.lastname: Zeng
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Archacki
authors.forename: Tailan
authors.initials: T
authors.lastname: Zhan
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D010649:Phenylalanine; D007930:Leucine