Linkage of a new locus for autosomal recessive axonal form of Charcot-Marie-Tooth disease to chromosome 8q21.3

Abstract

We report the clinical and genetic linkage analysis of a large Tunisian family with thirteen affected patients suffering from Charcot-Marie-Tooth disease with pyramidal involvement. The inheritance is autosomal recessive. The clinical phenotype is consistent in all patients. It is characterized by onset during the first decade, a progressive course and distal atrophy in all four limbs, associated with a mild pyramidal syndrome. Nerve biopsy in two patients showed severe axonal neuropathy. Genetic linkage excluded known loci of different genetic forms of Charcot-Marie-Tooth disease, familial spastic paraplegia and familial amyotrophic lateral sclerosis. A significant lod score was obtained with marker D8S286, confirming linkage to chromosome 8q21.3. The clinical syndrome observed in this family seems to correspond to a new genetic form of autosomal recessive Charcot-Marie-Tooth disease.