[Analysis of the GABRG2 gene mutation in a Chinese family with generalized epilepsy with febrile seizures plus].
OBJECTIVE
To identify the mutation of the GABA(A)-receptor gamma 2 subunit gene (GABRG2) in a Chinese family with generalized epilepsy with febrile seizures plus (GEFS+ ) and analyze the genotype-phenotype correlations and its inheritance.


METHODS
Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS+ family. The coding regions and flanking intronic regions of the GABRG2 gene were screened for mutations using polymerase chain reaction (PCR) and direct DNA sequencing.


RESULTS
There were 7 affected members in the three-generation family, in which one with febrile seizures (FS) and six with febrile seizures plus (FS+ ). This family was consistent with the diagnostic criteria of GEFS+ . The nonsense mutation c.1287G to A (p.W390X) in the GABRG2 gene was initially identified in the proband. Seven affected members (6 FS+ and 1 FS) and one unaffected member carried the mutation. The nonsense mutation c.1287G to A/p.W390X in the GABRG2 gene was co-segregated with the GEFS+ family. The penetrance rate was about 87.5%(7/8).


CONCLUSIONS
This GEFS+ family was consistent with autosomal dominant inheritance with incomplete penetrance. GABRG2 mutation is also a disease-causing mutation in Chinese GEFS+ patients. The p.W390X mutation has not been reported previously.
Sun
Huihui
H
Department of Pediatrics, the First Hospital, Peking University, Beijing, 100034 P. R. China.
Zhang
Yuehua
Y
Liu
Xiaoyan
X
Ma
Xiuwei
X
Wu
Husheng
H
Xu
Keming
K
Qi
Yu
Y
Wu
Xiru
X
D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000150:complications* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics*; D003294:Seizures, Febrile / Q000150:complications* / Q000235:genetics*
C546279:GABRG2 protein, human; D011963:Receptors, GABA-A