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A Founder Mutation in French-Canadian Families with X-linked Hereditary Neuropathy

Published online by Cambridge University Press:  02 March 2017

Nicolas Dupré ,
Louise Cossette ,
Collette K. Hand ,
Jean-Pierre Bouchard ,
Guy A Rouleau  and
Jack Puymirat
Nicolas Dupré
Affiliation:
Laboratoire de Recherche en Génétique Humaine, CHU Laval, Canada
Louise Cossette
Affiliation:
Laboratoire de Recherche en Génétique Humaine, CHU Laval, Canada
Collette K. Hand
Affiliation:
Center for Research in Neuroscience, McGill University and the Institut de Recherche, Hôpital Général de Montréal, Montréal, Canada
Jean-Pierre Bouchard
Affiliation:
Département des Sciences Neurologiques, Hôpital Enfant-Jésus, QuébecCanada
Guy A Rouleau
Affiliation:
Center for Research in Neuroscience, McGill University and the Institut de Recherche, Hôpital Général de Montréal, Montréal, Canada
Jack Puymirat*
Affiliation:
Laboratoire de Recherche en Génétique Humaine, CHU Laval, Canada
*
Laboratoire de Recherche en Génétique Humaine, CHU Laval, 2705 Blvd Laurier, Ste-Foy, Québec, G1V4G2, Canada.
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Abstract:

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Background:

The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX).

Methods:

Molecular analysis was performed by nonisotopic 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 one family, the mutation Arg142Trp was located in the transmembrane domain III 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 founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demyelination.

Conclusion:

Our study suggests that the Ser26Trp mutation may cause a primary demyelinating neuropathy that is not associated with a specific clinical phenotype. We also find evidence that the majority of kindreds share a common ancestor.

Résumé:

RÉSUMÉ:Introduction:

Le but de cette étude était d'identifier les mutations du gène de la connexine 32 chez des familles canadiennes-françaises atteintes de la maladie de Charcot-Marie-Tooth liée à l'X (CMTX).

Méthodes:

L'analyse moléculaire a été faite par polymorphisme de conformation d'ADN simple brin non isotopique et séquençage. L'évaluation clinique a été effectuée selon l'échelle définie par le Consortium HMSN Européen.

Résultats:

Dans une famille, la mutation Arg142Trp a été localisée dans le domaine transmembranaire III alors que chez quatre autres familles, nous avons identifié une nouvelle mutation (Ser26Trp) localisée dans le domaine transmembranaire I du gène Cx32. L'analyse des haplotypes a montré que ces quatre familles sont apparentées et suggère qu'il s'agit d'une mutation fondatrice. Seize patients de ces quatre familles ont été étudiés. Tel que prévu, tous les hommes atteints étaient plus sévèrement atteints que les femmes et tous les patients atteints présentaient des caractéristiques électrophysiologiques de démyélinisation.

Conclusion:

Notre étude suggère que la mutation Ser26Trp peut causer une neuropathie démyélinisante primaire qui n'est pas associée à un phénotype clinique spécifique. Nous avons également des données qui démontrent que la majorité des familles ont un ancêtre commun.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 28 , Issue 1 , February 2001 , pp. 51 - 55
Copyright
Copyright © The Canadian Journal of Neurological 2001

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