Constant rearrangement of the CMT1A-REP sequences in HNPP patients with a deletion in chromosome 17p11.2: a study of 30 unrelated cases

HNPP results predominantly from a deletion within chromosome 17p11.2 which corresponds to the CMT1A duplicated region (CMT1A/HNPP monomer unit) or, in rare cases, from a frame shift mutation in the PMP22 gene located in this interval. It has been postulated that the deleted chromosome in HNPP and the duplicated chromosome in CMT1A are the reciprocal products of an unequal crossing-over. The existence of the CMT1A-REP, two homologous sequences flanking the 1.5 Mb CMT1A/HNPP monomer unit, probably accounts for this phenomenon. The observation of three HNPP patients with a deletion of a part of the distal CMT1A-REP confirmed this hypothesis. In order to evaluate the frequency of 17p11.2 deletion involving a rearrangement in the CMT1A-REP, EcoRI digested DNA from 30 unrelated patients with HNPP was analyzed by hybridization with appropriate probes.