A founder mutation in French-Canadian families with X-linked hereditary neuropathy

Background: The aim of the present study was to identify the mutations in t he connexin 32 gene in French-Canadian families with X-linked Charcot-Marie -Tooth disease (CMTX). Methods: Molecular analysis was performed by nonisot opic single strand conformation polymorphism (SSCP) analysis and sequencing . Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium. Results: In o ne family, the mutation Arg142Trp was located in the transmembrane domain I II whereas, in four other families we identified a novel mutation (Ser26Trp ) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a found er mutation. Sixteen patients from these four families were studied. As exp ected, all the affected males were more clinically affected than the female s and all affected patients exhibited some electrophysiological characteris tics of demyelination, Conclusion: Our study suggests that the Ser26Trp mut ation may cause a primary demyelinating neuropathy that is not associated w ith a specific clinical phenotype. We also find evidence that the majority of kindreds share a common ancestor.