Recombination hot spot in a 3.2-kb region of the Charcot-Marie-Tooth type 1A repeat sequences: new tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A. French CMT Collaborative Research Group.

摘要: Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, duplications deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements reciprocal products an unequal meiotic crossover between chromosome 17 homologues, caused by misalignment CMT1A repeat sequences (CMT1A-REPs), homologous flanking CMT1A/HNPP monomer unit. In order map recombination breakpoints within CMT1A-REPs, a 12.9-kb restriction was constructed from cloned EcoRI fragments proximal distal CMT1A-REPs. Only 3 tested sites were present in CMT1A-REP but absent CMT1A-REP, indicating high degree homology these sequences. The mapped four regions CMT1A-REPs analysis 76 index cases 38 HNPP patients, who where unrelated. A hot spot breakpoints, located 3.2-kb region, accounted for three-quarters rearrangements, detected after EcoRI/SacI digestion, presence 7.8-kb junction respectively. fragments, which can be classical Southern blots, permit molecular diagnosis. Other also gene dosage blots.