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

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Muscle Nerve. 2008 Oct 23;38(5):1510-1514.

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

Baker SK, Reith CC, Ainsworth PJ.

Department of Medicine, Division of Neurology, Neuromuscular Disease

Clinic, McMaster University Medical Center, 120 Main Street West,

Hamilton, Ontario L8N 3Z5, Canada.

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.