Facilitated diagnosis of CMT1A duplication in chromosome 17p11.2-12: analysis with a CMT1A-REP repeat probe and photostimulated luminescence imaging.

Charcot-Marie-Tooth disease type 1A (CMT1A) is a common autosomal dominant demyelinating peripheral neuropathy. Most patients with CMT1A have been found to have a 1.5 megabase tandem DNA duplication in chromosome 17p11.2-12. Meiotic unequal crossover mediated by the CMT1A-REP repeat is a proposed mechanism for generation of the duplication in CMT1A and a reciprocal deletion seen in hereditary neuropathy with liability to pressure palsies. Testing for the CMT1A duplication is frequently the first step in the molecular diagnosis of patients with suspected inherited demyelinating neuropathy. We used a 1.0 kb EcoRI-PstI DNA fragment (pHK1.0P) from the proximal CMT1A-REP repeat as a probe for Southern blot analysis and detected increased gene dosage in CMT1A by determining measuring radioactivity ratios with a photostimulated luminescence imaging plate. We found that this method is useful for rapid diagnosis of the DNA duplication associated with CMT1A.