[A case of hereditary motor and sensory neuropathy type I with a new type of peripheral myelin protein (PMP)-22 mutation].

A 16-year-old school boy suffered from an insidious foot deformity. Slight degrees of symmetrical muscular weakness of the distal lower limb muscles were observed. In addition, slight degrees of atrophy of the anterior tibial muscles with moderate degrees of pes cavus deformity and flexion contracture of the toes of both feet were observed. In the upper and lower limbs muscle stretch reflexes were decreased and absent, respectively. Vibratory and touch sensations were moderately and slightly decreased, respectively, in the toes. The median and ulnar motor conduction velocities (m/sec) were 21.1 and 13.2, respectively, with markedly prolonged distal latencies. The median and ulnar sensory conduction velocities (m/sec) were 21.5 and 10.1, respectively. No M-waves were recorded by stimulation of the tibial and peroneal nerves. Also no nerve action potential was elicited by stimulation of the sural nerve. A fascicular biopsy of the sural nerve was performed. The myelinated fibers showing segmental de- and re-myelination were frequently found in teased fiber preparations. The density of myelinated fibers was markedly decreased, and both demyelinated axons and onion-bulbs were also observed by light and electron microscopy in the Epon-embedded sections. Based on the neurological examination and nerve conduction studies, although other family members were not examined, a diagnosis of HMSN type I was made. To clarify the genetic abnormality, a systematic study of the genomic DNA was made. A DNA duplication in the chromosome 17p11.2-12 was not observed. The single-strand conformational polymorphism method showed an abnormal extra band in the exon 3 encoding peripheral myelin protein (PMP)-22 gene of the patient compared with the control. The direct sequencing analysis of the exon 3 revealed a guanine to cytosine substitution that caused a substitution of arginine for glycine at amino acid position 93 of PMP-22. The digestion of the exon 3 with Sty I showed the presence of a mutant and normal allele of the PMP-22 gene indicating autosomal dominant heredity. This type of PMP-22 gene mutation is different from any type of PMP-22 mutations reported in the literature. The mutation is located in the intracellular domain of PMP-22. The mechanism by which the mutation induce demyelination of the peripheral myelin remains to be elucidated. Reports of patients with a point mutation of amino acids of PMP-22 are rare in the literature. This is the first Japanese patient with a new type of mutation of the PMP-22 gene.