[Phenotypic heterogeneity in Japanese Charcot-Marie-Tooth disease type 1A patients with PMP-22 gene duplication].
We studied phenotypic heterogeneity in 18 Japanese patients with Charcot-Marie-Tooth disease type 1A (CMT1A) with PMP-22 gene duplication, together with heterogeneity of duplication size. In order to detect the duplication of PMP-22 gene region, the PMP-22 cDNA and a polymorphic marker VAW409R3 were used as probes for Southern blot analysis. As the clinical phenotypes, we assessed the degree of foot deformity, muscular weakness and atrophy, tendon reflexes, sensory impairment and electrophysiologic and sural nerve biopsy findings. Although the degree of muscular weakness and atrophy was slightly more severe in the advanced age, there was a patient with calf hypertrophy in the older age or a patient with marked muscular atrophy of the leg in the younger age. The incidence of foot deformities and sensory impairment was high and these phenotypes did not relate to aging. Diminished or absent tendon reflexes and slowing of motor conduction velocities were commonly seen, but the motor conduction velocity varied greatly among the patients. The clinical phenotypes were extensively variable among the CMT 1A patients with the same gene mutation of PMP-22 gene duplication, suggesting that there is a factor other than PMP-22 gene duplication, which influences phenotypic manifestation in CMT 1A.