Locations of crossover breakpoints within the CMT1A-REP repeat in Japanese patients with CMT1A and HNPP

Abstract

The crossover breakpoints for Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are located in the CMT1A-REP repeat flanking a 1.5-Mb region of chromosome 17p11.2–12. The precise locations of the breakpoints are heterogeneous, and we analyzed the relative frequency distribution of breakpoints in 33 unrelated Japanese CMT1A and 3 unrelated HNPP families. The CMT1A-REP repeat region was divided into five regions, A, B, C, D and E, based on restriction site differences between the proximal and distal CMT1A-REP repeats. The frequency distribution of breakpoints within the CMT1A-REP repeat in the Japanese patients was 3% in region A, 78% in B/C and 19% in D, which is similar to that in Caucasian patients. This result also indicates that an 8-kb region defined by region B/C is a recombinational hotspot within the CMT1A-REP repeat in Japanese patients.