Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q)

Objective: To report a family with X-linked Charcot-Marie-Tooth disease (CM TX) with proven connexin 32 (Cx32) mutation associated with deafness. Metho ds: Twelve members of a CMTX family were examined clinically. Electromyogra phy and sensory and motor conduction studies were performed in three men, t wo women, and a 7-year-old boy. Audiometric testing was carried out in the three men, one woman, and an 8-year-old girl. Molecular genetic analysis wa s performed in six men and five women. Results: The three men and the 7-yea r-old boy had the usual sensorimotor deficit and pronounced reduction of mo tor nerve conduction velocity. A 15-year-old boy was asymptomatic and had o nly areflexia. The women had impairment of vibratory sensation and slight s lowing of nerve conduction velocities. Sensorineural deafness was observed in the three men and in an 8-year-old girl without any motor or sensory def icit. Molecular genetic analysis revealed a new missense mutation located i n codon 142 of the Cx32 gene leading to the substitution of an arginine by a glutamine. Conclusion: CMTX due to Cx32 mutations often shows interfamili al and intrafamilial phenotypic variation, which is also the hallmark of th is family. The sensorineural deafness observed in this family suggests that Cx32 could play an important role in the auditory pathway.