Clustering of CMT1A duplication breakpoints in a 700 bp interval of the CMT1A-REP repeat.

Abstract

The CMT1A-REP repeat is proposed to mediate unequal crossover leading to a 1.5 Mb duplication in chromosome 17p11.2-12 associated with Charcot-Marie-Tooth neuropathy type 1A (CMT1A). There is an apparent recombinational "hotspot" in the CMT1A-REP repeat since the majority of crossover breakpoints for CMT1A are located within a 1.7 kb interval. Further to characterize the crossover breakpoint region, we constructed PCR primers that specifically amplify the duplication breakpoint junctions in a series of Japanese and Caucasian CMT1A patients. We mapped the breakpoints in 89% of patients within a 700 bp interval of the CMT1A-REP repeat. This 700 bp region is 1.3 kb telomeric to a previously described mariner-like transposable element. Our observations further define the location of crossovers for CMT1A and provide additional evidence that this region is a recombinational "hotspot" within the CMT1A-REP repeat.