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A Novel GDAP1 Mutation 439delA is Associated with Autosomal Recessive CMT Disease

Published online by Cambridge University Press:  02 December 2014

Domna-Maria Georgiou ,
Paschalis Nicolaou ,
David Chitayat ,
Pantelitsa Koutsou ,
Riyana Babul-Hirji ,
Jiri Vajsar ,
Jillian Murphy  and
Kyproula Christodoulou
Domna-Maria Georgiou
Affiliation:
Molecular Genetics Department D, The Cyprus, Institute of Neurology and Genetics, Nicosia, Cyprus
Paschalis Nicolaou
Affiliation:
Molecular Genetics Department D, The Cyprus, Institute of Neurology and Genetics, Nicosia, Cyprus
David Chitayat
Affiliation:
Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Pantelitsa Koutsou
Affiliation:
Molecular Genetics Department D, The Cyprus, Institute of Neurology and Genetics, Nicosia, Cyprus
Riyana Babul-Hirji
Affiliation:
Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Jiri Vajsar
Affiliation:
Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Jillian Murphy
Affiliation:
Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
Kyproula Christodoulou*
Affiliation:
Molecular Genetics Department D, The Cyprus, Institute of Neurology and Genetics, Nicosia, Cyprus
*
Molecular Genetics Department D, The Cyprus Institute of Neurology and Genetics, 6 International Airport Ave., P.O. Box 23462, 1683 Nicosia, Cyprus.
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Abstract

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Background:

Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Based on neurophysiological and neuropathological criteria CMT has been sub-classified into two main types: demyelinating and axonal. Furthermore, it is genetically heterogeneous with autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance. Thus far, seven genes have been identified in association with the demyelinating AR-CMT disease. We hereby report our clinical and molecular genetic findings in a consanguineous family with AR-CMT.

Methods:

Two young sisters with AR-CMT and other non-affected family members were clinically and electrophysiologically evaluated and then molecular genetic investigation was carried out in order to identify the pathogenic mutation.

Results:

Following an initial indication for linkage of the family to the CMT4A locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and identified a single nucleotide deletion in exon 3 that is associated with AR-CMT in the family.

Conclusion:

We identified a novel GDAP1 439delA mutation that is associated with AR-CMT in a consanguineous family of Iranian descent with two affected young girls and a history in other members of the family.

Résumé:

RÉSUMÉ:Contexte:

La maladie de Charcot-Marie-Tooth (CMT) est la forme la plus fréquente de neuropathie sensitivomotrice héréditaire. La maladie de CMT a été sous divisée en deux types principaux, le type démyélinisant et le type axonal, selon des critères neurophysiologiques et neuropathologiques. De plus, la maladie est hétérogène au point de vue génétique avec hérédité dominante autosomique, récessive autosomique (RA) et liée à l’X. Jusqu‘à maintenant, sept gènes associés à la maladie de CMT-RA démyélinisante ont été identifiés. Nous rapportons nos observations cliniques et moléculaires chez une famille consanguine atteinte de maladie de CMT-RA.

Méthodes:

Deux jeunes soeurs atteintes de maladie de CMT-RA et les membres non atteints de la famille ont subi une évaluation clinique et électrophysiologique ainsi qu’une étude de génétique moléculaire afin d’identifier la mutation en cause.

Résultats:

Les études initiales indiquaient un linkage au locus CMT4A sur le chromosome 8 dans la famille. Nous avons donc séquencé le gène GDAP1 et nous avons identifié une délétion d’un seul nucléotide dans l’exon 3 associée au CMT-RA dans cette famille.

Conclusions:

Nous avons identifié une nouvelle mutation, 439delA dans le gène GDAP1, associée au CMT-RA dans une famille consanguine de descendance iranienne ayant une histoire familiale positive et dont deux jeunes filles sont atteintes de la maladie.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 33 , Issue 3 , August 2006 , pp. 311 - 316
Copyright
Copyright © The Canadian Journal of Neurological 2006

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