Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough

Abstract

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12–q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22–p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of < − 3 on both 3p12–q13 and 3p22–p24. Mutation scanning of the entire coding regions of the MPZ and PMP22 genes revealed no mutations. We conclude that the disorder described here is a newly classified hereditary motor and sensory neuropathy with autosomal dominant inheritance.