The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs

The CMT1A-REPs are two large directly repeating DNA sequences located on chromosome 17p11.2-p12 flanking the region duplicated in patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and deleted in patients with hereditary neuropathy with liability to pressure palsies (HNPP), We have sequenced two cosmids, c74F4 and c15H12, which contain the entire proximal and distal CMT1A-REPs and determined that these repeats are similar to 99% identical across a 24011 bp region, In addition, both contain an exon of the human heme A:faunesyltransferase gene (COX10), Hybridization studies revealed that COX10 spans the distal CMT1A-REP, while the proximal CMT1A-REP contains an isolated COX10 'pseudo-exon', There is also a COX10 hybridization signal on chromosome 10 which appears to represent a processed pseudogene, We propose that the distal CMT1A-REP represents the progenitor copy of COX10 exon VI which was duplicated with surrounding intronic sequences during mammalian genome evolution and that the HNPP deletion results in a COX10 null allele.