A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element

The Charcot-Marie Tooth disease type 1A (CMT1 A) duplication and hereditary neuropathy with liability to pressure palsies (HNPP) deletion are reciprocal products of an unequal crossing-over event between misaligned flanking CMT1A-REP repeats. The molecular aetiology of this apparently homologous recombination event was examined by sequencing the crossover region. Through the detection of novel junction fragments from the recombinant CMT1 A-REPs in both CMT1A and HNPP patients, a 1.7-kb recombination hotspot within the ∼30-kb CMT1 A-REPs was identified. This hotspot is 98% identical between CMT1 A-REPs indicating that sequence identity is not likely the sole factor involved in promoting crossover events. Sequence analysis revealed a mariner transposon-like element (MITE) near the hotspot which we hypothesize could mediate strand exchange events via cleavage by a transposase at or near the 3′ end of the element.