Charcot-Marie-Tooth (CMT) disease is the most com­mon inherited disorder of the peripheral nervous system. It is a genetically and clinically heterogeneous group of disorders with a prevalence of 1 in 2,500. The majority of CMT1 cases have 1.5 Mb duplication in chromosome 17p11.2 (CMT1A), while most patients with a clinically different neuropathy [hereditary neuropathy with liability to pressure palsies (HNPP)] have a deletion of the same region. The CMT1A duplication and HNPP deletion are reciprocal products of an unequal crossover event occurring in the critical region on chromosome 17. Altogether, they are responsible for the defects in about 80% of autosomal-dominant CMT cases.

We have analyzed a total of 57 CMT1 families with autosomal-dominant inheritance. All family members were investigated using markers D17S921 and D17S122, closely linked to the CMT1 region, on an ALF Express Fragment analyzer. This approach was informative in 88% of cases. We have detected 12 families with the CMT1A duplication and five with the HNPP deletion. In all of these the polymorphic results were confirmed using Southern blot analyses. We have observed reliable and reproducible gene dosage differences in affected subjects and normal controls.

This allowed us to perform correct and fast molecular diagnosis in the great majority of Bulgarian CMT1A and HNPP cases.

Key Words: Charcot-Marie-Tooth (CMT), CMT1A duplication, hereditary neuropathy with liability to pressure palsies (HNPP), polymorphic analysis