Résumé :
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Mutations in GDAP1 gene located in 8q13 chromosome have been identified in families with either axonal or demyelinating form of autosomal recessive Charcot-Marie-Tooth (CMT) disease. Twenty five patients belonging to 14 Moroccan consanguineous families were examined clinically and electrophysiologically. In one patient, a peroneal nerve biopsy was performed. Linkage to 8q13 was then demonstrated and a mutation in the coding region of the GDAP1 gene was identified by direct sequencing. Neuropathy was evident during early childhood, walking was delayed in 5 cases and onset of symptoms occurred before 6 years in the others. The phenotype was very severe: foot deformities and disability involving the hands and feet developed towards the end of the first decade and followed by involvement of proximal muscles in the lower limbs leading to loss of autonomy in 16 cases. Only three patients had hoarse voice. Thirteen patients belonging to 7 families were homozygous for the S194X mutation of GDAP1. They all had axonal form of CMT according to electrophysiological and morphological findings. Six patients belonging o 3 families had either homozygous P78L mutation or compound heterozygous P78L/S194X mutations. Most of them had markedly reduced motor nerve conduction velocity ranging from 11 to 34 m/s consisting with a demyelinating form of CMT. For the remaining 6 patients belonging to 3 families, GDAP1 mutation has not been identified yet. The main phenotype characteristics of GDAP1 mutations are: early onset in childhood, severity and important foot deformities. The homozygous S194X mutation is the most frequent in our families and was related to axonal form of CMT suggesting a probable founder effect and a possible phenotype/genotype correlation.
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