Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation.

BACKGROUND The MPZ Thr124Met mutation is characterised by a late onset, pupillary abnormality, deafness, normal or moderate decreased motor nerve conduction velocity, and axonal damage in sural nerve biopsy. OBJECTIVE To investigate the clinical manifestations of the axonal or demyelinating forms of the Japanese MPZ Thr124Met mutation originating in four different areas: Tottori, Nara, Aichi, and Ibaragi. RESULTS Genotyping with DNA microsatellite markers linked to the MPZ gene on chromosome 1q22-q23 showed shared allelic characteristics between 12.65 cM and revealed a common haplotype in all Tottori families. Aichi and Ibaragi families shared parts of the haplotype around the MPZ gene. However, there was no consistency with a Nara family. CONCLUSIONS The high frequency of this peculiar genotype in the Tottori CMT population is presumably due to a founder effect, but in Thr124 it might constitute a mutation hotspot in the MPZ gene.