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A Novel GDAP1 Mutation P78L Responsible for CMT4A Disease in Three Moroccan Families

Published online by Cambridge University Press:  02 December 2014

Ahmed Bouhouche ,
Nazha Birouk ,
Ali Benomar ,
Reda Ouazzani ,
Taïeb Chkili  and
Mohamed Yahyaoui
Ahmed Bouhouche
Affiliation:
Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, Rabat, Morocco
Nazha Birouk
Affiliation:
Service de Neurophysiologie Clinique, Hôpital des Spécialités, Rabat, Morocco
Ali Benomar
Affiliation:
Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, Rabat, Morocco
Reda Ouazzani
Affiliation:
Service de Neurophysiologie Clinique, Hôpital des Spécialités, Rabat, Morocco
Taïeb Chkili
Affiliation:
Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, Rabat, Morocco
Mohamed Yahyaoui
Affiliation:
Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, Rabat, Morocco
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Abstract

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Background:

The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both axonal and demyelinating neuropathy. Up to date, 25 mutations in the GDAP1 gene have been reported in patients from different origins.

Methods:

Three Moroccan families with early onset ARCMT1 and autosomal recessive inheritance were genotyped to test linkage to 8q21.3 and their GDAP1 gene coding exons screened for mutations.

Results:

A novel C233T transversion at codon 78 (P78L) was detected in 6 patients from 3 unrelated families. The mutation was found to be homozygous in two families and compound heterozygous in association with the already reported S194X mutation in one family. The P78L mutation was associated with a common haplotype suggesting a Moroccan founder mutation. The patients had symptoms within the two first years of life and developed common phenotype of CMT4A with evident hoarse-voice in two cases with the longer disease duration.

Conclusion:

P78L mutation was associated with a common haplotype suggesting a common ancestor.

Résumé:

RÉSUMÉ:<span class='italic'><span class='bold'>Contexte</span></span>:

Le gène qui code pour la protéine GDAP1 (ganglioside-induced-differentiationassociated protein 1) a été associé à une neuropathie axonale démyélinisante. Jusqu’à maintenant, 25 mutations du gène GDAP1 ont été rapportées chez des patients de différentes origines ethniques.

<span class='italic'><span class='bold'>Méthodes</span></span>:

Trois familles marocaines, atteintes d’une ARCMT1 à début précoce et dont l’hérédité était autosomique récessive, ont été génotypées pour déterminer s’il existait une liaison à la région 8q21.3 et on a recherché des mutations dans les exons codants du gène GDAP1.

<span class='italic'><span class='bold'>Résultats</span></span>:

Une nouvelle transversion C233T au codon 78 (P78L) a été décelée chez 6 patients appartenant à 3 familles non apparentées. Il s’agissait d’une mutation à ’état homozygote dans deux familles et à l’état hétérozygote composé en association à une mutation S194X dans l’autre famille. Cette mutation a déjà été rapportée dans une famille. La mutation P78L est associée à un haplotype commun, ce qui laisse croire qu’il s’agit d’une mutation fondatrice marocaine. Les patients présentaient des symptômes au cours des deux premières années de vie et par la suite le phénotype habituel de la CMT4A. Une voix rauque a été observée chez deux patients atteints depuis longtemps.

<span class='italic'><span class='bold'>Conclusion</span></span>:

La mutation P78L est associée à un haplotype commun, ce qui porte à croire qu’elle provient d’un ancêtre commun.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue 4 , November 2007 , pp. 421 - 426
Copyright
Copyright © The Canadian Journal of Neurological 2007

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