A NEW-TYPE OF HEREDITARY MOTOR AND SENSORY NEUROPATHY LINKED TO CHROMOSOME-3

We report the clinical, pathological, and genetic findings of 23 patie nts in 8 families with hereditary motor and sensory neuropathy (proxim al dominant form) (HMSN-P) in Okinawa, Japan. The clinical features we re unique with respect to autosomal dominant inheritance, Kennedy-Alte r-Sung syndrome-like proximal dominant neurogenic-atrophy, obvious sen sory involvement, painful muscle cramp, fasciculations, areflexia, and high incidences of elevated creatine kinase levels, hyperlipidemia, a nd diabetes mellitus. Electrophysiological and pathological studies re vealed typical motor and sensory axonal neuropathy, and decreased numb ers of anterior horn and dorsal ganglion cells, which suggested the pr esence of neuronopathy in HMSN-P. Genetic linkage studies showed a lod score of 4.04 (two-point analysis) in DNA marker D3S1284. Haplotype a nalysis showed that the gene locus of the disease was mapped to 3p14.1 -q13 bracketed by D3S1285 and D3S1281. In this region, the patients' c hromosomes showed an obvious increase in the allele frequency of five markets. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the p resence of linkage disequilibrium and a common origin of this allele i n all patients with HMSN-P. The HMSN-P described here is a new clinica l entity characterized by unique clinical manifestations and a new gen e locus.