[The diagnosis and prevalence of locus CMT1A duplication in Charcot-Marie-Tooth disease type 1]

Abstract

Background: The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) is the most frequent hereditary neuropathy. The demyelinated or type 1 form (CMT1) is the most frequently presented, commonly being of a dominant autosomic inheritance. CMT1 is heterogeneous genetically and the subjacent mutation found in most of the cases is a duplication of 1,500 kb in the CMT1A locus of chromosome 17p11.2. The aim of the present study was to determine the prevalence of CMT1A duplication in patients with CMT1 and evaluate its usefulness as a biological diagnostic marker.

Methods: The study was carried out in a group of patients with HMSN who were not related, and were distributed according to the following diagnostic categories: CMT1 (n = 49), CMT2 (n = 9), untyped CMT (n = 11) and Déjérine-Sottas (DS) disease (n = 4). To detect three alleles confirming the presence of duplication the DNA of the patients was analyzed with four polymorph markers, VAW409R3a, RM11-GT, VAW412R3HEc and EW401HE localized in the CMT1A locus.

Results: CMT1A duplication was found in 68.7% of the patients with CMT1 and in 27.2% of untyped CMT patients. None of the individuals in the CMT2 and DS categories showed duplication. Cases pertaining to families with dominant autosomic inheritance and genetically sporadic cases were confirmed to show a high prevalence of duplication, being of 83.3% and 85.7%, respectively.

Conclusions: Duplication of the CMT1A locus is the most prevalent mutation found in Charcot-Marie-Tooth type 1 disease. It is a specific mutation of this disease among the different forms of hereditary motor-sensitive neuropathy. This mutation is useful as a biological marker in the diagnosis of these neuropathies.