An 8-Generation Family With X-Linked Charcot-Marie-Tooth: Confirmation Of The Pathogenicity Of A 3 Untranslated Region Mutation In Gjb1 And Its Clinical Features

Introduction: Mutations in gap junction protein beta 1 (GJB1) on the X chromosome represent one of the most common causes of hereditary neuropathy. We assessed manifestations associated with a rare 3 untranslated region mutation (UTR) of GJB1 in a large family with X-linked Charcot-Marie-Tooth disease (CMTX). Methods: Clinical, electrophysiological, and molecular genetic analyses were performed on an 8-generation family with CMTX. Results: There were 22 affected males and 19 symptomatic females, including an 83-year-old woman followed for 40 years. Electrophysiological studies showed a primarily axonal neuropathy. The c.*15C>T mutation in the GJB1 3 UTR was identified in 4 branches of the family with a log of odds (LOD) of 4.91. This created a BstE II enzyme recognition site that enabled detection by restriction digestion. Discussion: The c.*15C>T mutation in the GJB1 3 UTR segregates with CMTX1 in 8 generations. Penetrance in males and females is essentially complete. A straightforward genetic method to detect this mutation is described. Muscle Nerve57: 859-862, 2018