[A familial Charcot-Marie-Tooth disease type 1B (CMTD1B) manifesting a new mutation of myelin P0 gene].

A 15-year-old girl (case 1) was admitted to our hospital because of progressive muscle weakness of the lower limbs and numbness of the upper limbs. She noted these symptoms beginning at 13 years of age. Neurological examination revealed that deep tendon reflexes were absent and hypesthesia of touch and pain sensation were distributed in a glove-and-stocking pattern. Muscle weakness and atrophy were predominantly present in the distal portions of the extremities. There were obvious pes cavus and champagne-bottle shape deformities. The motor conduction velocity of the median nerve was markedly delayed and sensory potentials were not evoked in any nerves examined. Lumbar MRI showed thickening of the nerve radices. Cranial MRI showed thickening of the acoustic nerves, as well. Histological studies of a biopsied sural nerve revealed a marked decrease in the number of myelinated and unmyelinated fibers and remarkable onion bulb formation. The patient's clinical manifestations and histological findings were more severe than that seen in the usual case of CMT1A. Her mother (case 2, 39 years old) had similar neurological and electrophysiological findings. DNA duplication encoding peripheral myelin protein 22, was not detected in either case 1 or 2. Sequencing of DNA from these patients revealed the presence of a mutant allele containing an A- to G-substitution of nucleotide 245, which replaced tyrosine with cysteine in the extracellular Ig-domain of the P0 protein.