SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus.
Generalized epilepsy with febrile seizures plus (GEFS+; MIM#604233) is a familial epilepsy syndrome characterized by phenotypic and genetic heterogeneity. It was associated with mutations in the neuronal voltage-gated sodium channel subunit gene (SCN1A, SCN2A, SCN1B) and ligand-gated gamma aminobutyric acid receptors genes (GABRG2, GABRD). We investigated the roles of SCN1A, SCN1B, and GABRG2 mutations in the etiology of Chinese GEFS+ families. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood lymphocytes of 23 probands and their family members. The sequences of SCN1A, SCN1B, and GABRG2 genes were analyzed by polymerase chain reaction (PCR) and direct sequencing. The major phenotypes of affected members in the 23 GEFS+ families exhibited FS and FS+, whereas rare phenotypes afebrile generalized tonic-clonic seizures (AGTCS), myoclonic-astatic epilepsy (MAE), and partial seizures were also observed. A novel SCN1A mutation, p.N935H, was identified in one family and another novel mutation in GABRG2, p.W390X, in another family. However, no SCN1B mutation was identified. The combined frequency of SCN1A, SCN1B, and GABRG2 mutations was 8.7% (2/23), extending the distribution of SCN1A and GABRG2 mutations to Chinese GEFS+ families. There were still unidentified genes contributing to the pathogenesis of GEFS+.
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Huihui
H
Sun
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China. zhangyhd@bjmu.edu.cn.
Yuehua
Y
Zhang
Jilin University, First Hospital, Changchun, 130021, China.
Jianmin
J
Liang
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Xiaoyan
X
Liu
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Xiuwei
X
Ma
Beijing Children's Hospital, Beijing, 100045, People's Republic of China.
Husheng
H
Wu
Capital Institute of Pediatrics, Beijing, 100020, People's Republic of China.
Keming
K
Xu
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Jiong
J
Qin
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Yu
Y
Qi
Peking University, First Hospital, No. 1 Xian Men Street, Xicheng District, Beijing, 100034, People's Republic of China.
Xiru
X
Wu
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
C546279:GABRG2 protein, human; D008024:Ligands; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011963:Receptors, GABA-A; C568242:SCN1A protein, human; C470379:SCN1B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit