A novel GDAP1 mutation P78L responsible for CMT4A disease in three Moroccan fami

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Can J Neurol Sci. 2007 Nov;34(4):421-6.

A novel GDAP1 mutation P78L responsible for CMT4A disease in three

Moroccan families.

Bouhouche A, Birouk N, Benomar A, Ouazzani R, Chkili T, Yahyaoui M.

Service de Neurologie et de Neurogénétique, Hôpital des Spécialités,

BP 6402, Al Irfane Rabat, Morocco.

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.