LINKAGE OF A LOCUS (CMT4A) FOR AUTOSOMAL RECESSIVE CHARCOT-MARIE-TOOTH DISEASE TO CHROMOSOME-8Q

Autosomal recessive Charcot - Marie - Tooth (CMT) disease (CMT4) is a complex group of severe childhood motor and sensory neuropathies, char acterized by an early age of onset with rapidly progressive distal lim b weakness and atrophy. One subgroup designated CMT4 type A (CMT4A) wa s selected from a series of Tunisian CMT4 families according to the fo llowing electrophysiological and pathological criteria: slow motor ner ve conduction velocity (MCV), severe hypomyelination upon nerve biopsy with basal lamina onion bulbs and no myelin outfolding. In an attempt to localize the CMT4A locus, we studied four inbred families with 13 affected patients. Significant evidence for linkage was found for seve ral markers from chromosome 8q13 - 21.1 (D8S279, D8S164, D8S286, D8S84 , D8S275 and D8S167). An overall two point peak lod score of z(theta)= 9.19 at theta=0.00 (95% confidence limit 0.00 - 0.08) was obtained for D8S164. No evidence of genetic heterogeneity was found. The chromosom al localization of one form of CMT4 will have important implications i n clarifying the nosology of this complex group of disorders.