Clinical &molecular analysis of X-linked CMT 1 in Spanish population

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Clin Genet. 2006 Dec;70(6):516-23.

Clinical and molecular analysis of X-linked Charcot-Marie-Tooth

disease type 1 in Spanish population.

Casasnovas C, Banchs I, Corral J, ez-Matos J, Volpini V.

Neuromuscular Unit, Neurology Department, Hospital Universitari de

Bellvitge-IDIBELL, Feixa Llarga s/n.

From 1995 to 2004, 979 families with hereditary peripheral

neuropathy were referred to the Genetic Diagnosis Center. Using

single-strand conformation analysis (SSCA), the connexin 32 gene was

analysed in all the patients from 498 families with sporadic or

dominant inheritance with no male-to-male transmission and absence

of the 17p2 duplication or deletion.

Affected males had pes cavus, distal leg weakness, muscular distal

atrophy, areflexia and distal sensory loss. The 106 families in

which SSCA revealed abnormal migration electrophoresis were directly

sequenced. We found 34 families (59 patients) with mutations in

connexin 32 gene.

In electrophysiological studies, 58.8% families presented slow and

14.7% intermediate nerve conduction velocities. Molecular findings

revealed that codon 164 (29.4 +/- 15.3%) and the second

extracellular (EC2) domain (44.1 +/- 16.6%) were the most frequently

affected codon and domain of the connexin 32.

Six novel mutations, Leu39fs, Glu47Gly, His153fs, Cys179Tyr,

Cys201Phe and Ser211fs, were found in our study.