Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation
Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation
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DOI：
10.1038/jhg.2011.69
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发表时间：
2011-08
影响因子：
3.5
通讯作者：
Su-Kyeong Hwang;Y. Makita;H. Kurahashi;Y. Cho;S. Hirose
中科院分区：
文献类型：
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作者：
Su-Kyeong Hwang;Y. Makita;H. Kurahashi;Y. Cho;S. Hirose
常染色体显性夜间额叶癫痫是一种家族性部分癫痫综合征，也是已知第一种与特定基因缺陷相关的人类特发性癫痫。临床可用的分子遗传学检测揭示了三个基因的突变，CHRNA 4，CHRNB 2和CHRNA 2。CHRNA 4的突变已在不同国家的家庭中发现; Ser 280 Phe在澳大利亚，西班牙，挪威和苏格兰家庭中，Ser 284 Leu在日本，韩国，波兰和黎巴嫩家庭中。其中没有报道建立者效应的明确证据，包括对澳大利亚和挪威家庭进行的单倍型研究。日本人和韩国人，因为他们的地理接近和历史的相互作用，显示出更大的遗传相似性比其他国家的人群中发现的突变Haplotype分析在两个以前报道的家庭，然而，独立的发生Ser 284 Leu突变。受影响的核苷酸是高度保守的，与CpG高变位点相关，而其他CHRNA 4突变不在突变热点。与CpG位点的关联解释了Ser 284 Leu突变的独立发生。
Autosomal dominant nocturnal frontal lobe epilepsy is a familial partial epilepsy syndrome and the first human idiopathic epilepsy known to be related to specific gene defects. Clinically available molecular genetic testing reveals mutations in three genes, CHRNA4, CHRNB2 and CHRNA2. Mutations in CHRNA4 have been found in families from different countries; the Ser280Phe in an Australian, Spanish, Norwegian and Scottish families, and the Ser284Leu in a Japanese, Korean, Polish and Lebanese families. Clear evidence for founder effect was not reported among them, including a haplotype study carried out on the Australian and Norwegian families. Japanese and Koreans, because of their geographical closeness and historical interactions, show greater genetic similarities than do the populations of other countries where the mutation is found. Haplotype analysis in the two previously reported families showed, however, independent occurrence of the Ser284Leu mutation. The affected nucleotide was highly conserved and associated with a CpG hypermutable site, while other CHRNA4 mutations were not in mutation hot spots. Association with a CpG site accounts for independent occurrence of the Ser284Leu mutation.