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 domi nant demyelinating peripheral neuropathy, Most patients with CMT1A hav e been found to have a 1.5 megabase tandem DNA duplication in chromoso me 17p11.2-12. Meiotic unequal crossover mediated by the CMT1A-REP rep eat is a proposed mechanism for generation of the duplication in CMT1A and a reciprocal deletion seen in hereditary neuropathy with liabilit y 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 fr agment: (pHKI,OP) from the proximal CMT1A-REP repeat as a probe for So uthern blot analysis and detected increased gene dosage in CMT1A by de termining measuring radioactivity ratios with a photostimulated lumine scence imaging plate. We found that this method is useful for rapid di agnosis of the DNA duplication associated with CMT1A. (C) 1997 Wiley-L iss, Inc.