Novel 95G>A (R32K) somatic mosaic connexin 32 mutation

Charcot-Marie-Tooth disease (CMT) is among the most common inherited disorders of the peripheral nervous system, and it is broadly categorized as demyelinating type 1 or axonal type 2 based on nerve conduction studies. Mutations in discrete genes usually segregate into a single phenotype. However, mutations in connexin 32 (Cx32) can produce both axonal and demyelinating CMT phenotypes. Although over 300 mutations have been described in Cx32, somatic mosaicism has only been reported once previously. We report a 39-year-old man who was referred for electrodiagnostic evaluation due to a history of bilateral carpal tunnel syndrome. His physical examination and electrodiagnostic findings demonstrated a mild sensorimotor axonal peripheral neuropathy. Sequencing of his Cx32 (GJB1) gene identified a guanine-to-adenine (G>A) transition at nucleotide position 95. This transition mutation involved approximately one-third of leukocyte-derived genomic DNA. This is the second reported case of somatic mosaicism, and it highlights the phenotypic diversity among CMTX patients.