Résumé :
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Hereditary motor and sensory neuropathies (HMSN), commonly referred to as Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurological diseases, with an overall prevalence of about 1-4/10,000. While all modes of inheritance have been reported, clinical, anatomopathological and particularly genetic heterogeneity have also already been underlined for this disease (more than 50 loci and 30 genes identified to date). The aim of this work was to investigate Algerian families for whom a clinical diagnosis of hereditary motor and sensory neuropathy has been suspected. Considering the high rate of consanguinity in Algeria, we focussed our analysis on families affected with autosomal recessive forms of the disease. The use of the strategy of homozygosity mapping, as well as a set of molecular tools, allowed us to explore a panel of 150 families and to characterize for some of them the molecular defect responsible of the observed phenotype, as well as the identification of a new locus whose gene has been further characterized. Thus, we could establish a precise molecular diagnosis for about 1/3 of the families, by characterizing mutations in several genes, MTMR2 (CMT4B1), GDAP1 (CMT4A), PRX (CMT4F), SH3TC2 (CMT4C), GAN (GAN) and LMNA (CMT2B1), whereas one new locus/gene could be identified (CMT4H/FGD4). Although molecular investigations are in progress for the remaining famlies, our results greatly reinforce the genetic heterogeneity already reported for CMT disease, and suggest that many other loci/genes have to be discovered. This study allowed us to estimate the relative frequency of autosomal recessive forms of CMT disease in our panel, to outline a certain geographical distribution for some CMT subtypes and to delineate the occurrence of recurrent mutations or founder effects. These observations are all important informations that will guide us to establish an efficient approach for diagnosis of autosomal recessive types of CMT disease in Algeria.
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