Mild phenotype of Charcot-Marie-Tooth disease type 4B1

Charcot-Marie-Tooth type 4B1 (CMT4B1) is a rare autosomal recessive demyelinating neuropathy caused by mutation of the myotubularin-related 2 (MTMR2) gene. It is characterized by a severe early-onset motor and sensory neuropathy, and myelin outfoldings on nerve biopsy. We describe a mild phenotype of CMT4B1 in a Japanese patient. She noticed difficulty in walking as an initial symptom at age 13. Her symptoms progressed slowly, and she could still walk at age 34. There was no cranial neuropathy. A nerve conduction study demonstrated demyelinating neuropathy. Sural nerve biopsy revealed a moderate-to-severe loss of myelinated fibers, and many focally folded myelin sheaths. Electron micrographs showed myelin outfoldings and infoldings. DNA tests for CMT showed that she is a homozygote for the MTMR2 p.R628PfsX18 mutation. The mild phenotype in our patient is probably due to the C-terminal position of the frame-shift mutation in MTMR2.