QUANTITATIVE MEASUREMENT OF DUPLICATED DNA AS A DIAGNOSTIC-TEST FOR CHARCOT-MARIE-TOOTH DISEASE TYPE-1A

Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and se nsory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the perip heral myelin protein PMP 22 (the critical gene in this subtype of CMT1 ) is located within this duplication. To detect this duplication in ch romosomal DNA from individuals thought to have CMT1, we compared the h ybridization signals of two DNA probes within this duplication (VAW412 R3a and VAW409R3a) with the signal of a reference probe (E3.9). When d uplication was present, the signals from the first two probes increase d from 100% (for nonduplicated samples) to 145% and 142%, respectively . The day-to-day variance was 3.7% and 5.1%, respectively. We demonstr ated this DNA duplication in 49 of 95 DNA samples from unrelated indiv iduals thought to have CMT1. Moreover, because hereditary neuropathy w ith liability to pressure palsies (HNPP) is based on a DNA deletion in the same area of chromosome 17, this quantitative test may be useful in establishing the presence of HNPP. In a preliminary investigation, four unrelated patients with HNPP yielded test values of 63% and 54%, respectively, of those for nonduplicated samples (CV 19% and 18%, resp ectively; n=4), suggesting a deletion in 17p11.2.