title: Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease.
abstract: Periaxin (PRX) plays an important role in the myelination of the peripheral nerve and consequently in the pathogenesis of Charcot-Marie-Tooth disease (CMT). To date, nine nonsense or frameshift PRX mutations have been reported in eight families with CMT. The patients with PRX mutations appeared to show characteristic clinical features with early onset but slow or no progression, a common result of mutations that lead to missing a C-terminal acidic domain. Here, we report a Japanese CMT patient with these characteristic clinical features, who was a compound heterozygote for PRX R1070X and L132FsX153 mutations. We previously reported that three Japanese isolated families also had the homozygous R1070X mutation. To examine the potential founder effect of the R1070X mutation in the Japanese population, we performed haplotype analysis and found that each R1070X allele lay on a different haplotype background in these four families. Therefore, the high frequency of the R1070X mutation among the Japanese population is not likely the consequence of a founder effect, but probably a result of a mutation hot spot.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
authors.forename: Tesshu
authors.initials: T
authors.lastname: Otagiri
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kijima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Arai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sawaishi
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Shimohata
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001369:Axons / Q000648:ultrastructure; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D018895:Microsatellite Repeats; D009035:Mothers; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D009692:Nucleic Acid Heteroduplexes; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; D009692:Nucleic Acid Heteroduplexes; C086745:periaxin; D004247:DNA