A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy

被引:171
作者
Hirose, S
Iwata, H
Akiyoshi, H
Kobayashi, K
Ito, M
Wada, K
Kaneko, S
Mitsudome, A
机构
[1] Fukuoka Univ, Sch Med, Dept Pediat, Jonan Ku, Fukuoka 8140180, Japan
[2] Shiga Med Ctr Children, Dept Pediat, Shiga, Japan
[3] Hirosaki Univ, Dept Neuropsychiat, Hirosaki, Aomori, Japan
关键词
autosomal dominant nocturnal frontal lobe epilepsy; neuronal nicotinic acetylcholine receptor alpha 4 subunit; epilepsy; channelopathy; neurotransmitter; nicotinic acetylcholine receptor;
D O I
10.1212/WNL.53.8.1749
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To identify the mutation responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a nonwhite family. Background: ADNFLE is newly recognized as an entity of idiopathic partial epilepsy. Recently, two different mutations of the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) gene were identified in a white family as a cause of ADNFLE, Methods: Four affected and three unaffected individuals in three generations of a Japanese family with ADNFLE, and 100 unrelated healthy Japanese volunteers were studied. Clinical features and EEG findings in affected individuals were consistent with those of ADNFLE reported in white families with ADNFLE. Mutations within the CHRNA4 gene were screened for using single-strand conformation polymorphism analysis (SSCA) and were determined by direct sequencing. The mutation identified was sought in volunteers by the amplification refractory mutation system. Results: A C-to-T exchange (C755T) was found in exon 5 of the CHRNA4 gene on one allele of affected individuals. C755T segregated in affected individuals and was not found in 200 alleles obtained from the volunteers. C755T replaced serine 252 (Ser(252)) in the second membrane-spanning domain (M2) of CHRNA4 with a leucine. Ser(252) is conserved characteristically in the alpha-subunit of acetylcholine receptor and is considered to play an important role in channel function. Conclusion: C755T is a novel missense mutation of the CHRNA4 gene causing autosomal dominant nocturnal frontal lobe epilepsy in this Japanese family.
引用
收藏
页码:1749 / 1753
页数:5
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