Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)

Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal domi-nant family with Charcot-Marie-Tooth axonal neuro-pathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe than of the feet with slow progressive course in 12 patients. Deep tendon reflexes were ab-sent in the upper extremities and decreased in the lower extremities. There was distal hypesthesia for touch, proprioception and vibration sense for the hands more than for the feet. Motor nerve conduction velocities showed normal values (48–53 M/s) with nor-mal latencies (2–3 msec) and electromyography re-vealed signs of denervation. Genetic linkage analysis used 167 short tandem repeat markers (STRPs) spaced throughout the 22 autosomes. Linkage to the short arm of chromosome 7 at 7p14 was found using the marker D7S435 (Z = 4.83 at θ = 0). Flanking markers were D7S1808 and D7S1806 and the genetic distance between them was 6.8 cM. The multipoint linkage analysis gave a peak multipoint lod score of 6.89 be-tween the markers D7S1808 and D7S435. Linkage analysis showed significantly negative lod scores (with values less than –2) with markers of chromo-somes 1 and 3 where CMT axonal forms have been previously mapped. PFGE analysis indicated the ab-sence of the CMT1A duplication. Our findings are con-sistent with a new genetic type of axonal CMT neuropathy designated by us as CMT2D. Potential candidate genes are multiple T-cell gamma receptor genes which map to the same cytogenetic interval as CMT2D neuropathy