title: Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation.
abstract: 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.
authors.affiliation: Department of Pediatrics, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, Japan.
authors.forename: Su-Kyeong
authors.initials: SK
authors.lastname: Hwang
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Cho
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics; D017034:Epilepsy, Frontal Lobe / Q000208:ethnology / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D007723:Korea; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic