Type 1 and mutations detected by DHPLA research from U of Verona

[Guest guest]

Research from J Peripher Nerv Syst. 2004 Jun;9(2):122.

Charcot-marie-tooth disease type 1: novel cases and novel mutations

detected by DHPLC.

Angiari C, Ferrarini M, Taioli F, Cavallaro T, Fabrizi G, Rizzuto N.

Department of Neurological and Visual Sciences, Section of Clinical

Neurology, University of Verona, Italy.

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.