Charcot‐marie‐tooth disease type 1: novel cases and novel mutations detected by DHPLC

Abstract

Background: Charcot‐Marie‐Tooth disease type 1 (CMT1) and related Dejerine‐Sottas syndrome (DSS) and Hereditary Neuropathy with liability to Pressure Palsy (HNPP) have a high degree of genetic heterogeneity; mutation analysis performed by direct nucleotide sequencing is highly sensitive but time‐consuming and expensive. Objective: To evaluate the sensitivity of denaturing high performance liquid chromatography (DHPLC), a recently developed technology for fast mutational analysis. Methods: Optimal conditions for analysing Cx32, P0 and PMP22 genes by DHPLC were developed on the basis of 39 mutations (Cx32 = 21; P0 = 10; PMP22 = 8) detected in the period 1997–2002. Patients: During 2003, 44 patients fitting the clinical and electrophysiological criteria of CMT1, DSS or HNPP who were negative for the 17p11.2 duplication/deletion were analysed either by nucleotide sequencing or by DHPLC. Results: In the last year we identified a total of 3 mutations in Cx32, 3 mutations in MP0 (2 novels mutations, one recessive) and 2 mutations in PMP22 (2 novels nonsense mutations). Conclusions: DHPLC was capable of detecting all mutations identified by sequencing, thus appearing as a reliable approach for the mutational analysis of CMT1.