[Heterogeneity in breakpoint location of duplication in Japanese Charcot-Marie-Tooth disease type 1A].

The crossover breakpoints for CMT1A are located in the CMT1A-REP repeat flanking a 1.5 Mb region of chromosome 17p11.2-12. We analysed the relationship between the breakpoint locations and clinical phenotypes in 21 Japanese patients with CMT1A duplication. The CMT1A-REP region was divided in 5 regions, A, B, C, D and E, based on restriction site differences between the proximal and distal CMT1A-REP repeats (Kiyosawa et al., HMG, 1995). The breakpoint location within the CMT1A-REP was heterogeneous, the frequency distribution of which was hightest in the B/C region and similar to that in Caucasian patients. The clinical phenotypes, such as foot deformity, muscular weakness and atrophy, sensory impairment and electrophysiologic finding, were extensively variable among the CMT1A patients with PMP22 gene duplication. The location of breakpoints was not related to the clinical phenotypes, suggesting that there is a factor other than the location of the crossover breakpoint, which influences phenotypic manifestation of CMT1A.