Periaxin mutation in Japanese CMT patients

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J Hum Genet. 2006 Jun 13

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth

disease.

Otagiri T, Sugai K, Kijima K, Arai H, Sawaishi Y, Shimohata M,

Hayasaka K.

Department of Pediatrics, Yamagata University School of Medicine, 2-2-

2 Iida-nishi, Yamagata, 990-9585, Japan.

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.