Dejerine-Sottas disease with a novel de novo dominant mutation, Ser 149 Arg, of the peripheral myelin protein 22

The Ser149Arg mutation of peripheral myelin protein 22 (PMP22) was found in a 19-year-old woman with a sporadic case of Dejerine-Sottas disease, The p atient showed delayed motor development. She walked for the first time with support at the age of 2 years. Scoliosis developed at age 4 years. Her wal king ability was best at age 11, Thereafter, she showed progressive muscle weakness and sensory disturbances in the distal extremities. At the age of is years, the use of a wheelchair became necessary. Motor and sensory nerve conduction studies showed absent motor and sensory responses on electrical stimulation of the limb nerves. A sural nerve biopsy specimen showed marke d decreases in the numbers of both large and small myelinated fibers, abund ant onion-bulb formation, and hypomyelination. Electron microscopic observa tion revealed the presence of demyelinated axons and myelin sheaths disprop ortionately thin relative to axon diameter. That this was a de novo mutatio n was established by parentage testing and PMP22 gene analysis of the paren ts. The mutation seems to be novel and dominant.