Charcot-Marie-Tooth type X: A novel mutation in the Cx32 gene with centralconduction slowing

Charcot-Marie-Tooth disease (CMT) is characterized by distal muscle weaknes s and wasting, often resulting in foot deformities and gait disturbancies, distal sensory impairment and by more or less typical changes in sural nerv e biopsy. CMT type 1 is also characterized by reduced nerve conduction velo cities. For these demyelinating subtypes, most frequently a 1.5 Mb tandem d uplication in chromosome 17p1 1.2-12 comprising the gene for the peripheral myelin protein 22 (PMP22) is observed (CMT1A), but point mutations in PMP2 2 have also rarely been reported. X-linked, dominant CMTX1 disease is the s econd most common type of these hereditary motor and sensory neuropathies ( HMSN). Mutations in the X chromosomal Gene Connexin32 (Cx32) synonymous gap junction beta -1 (GJB1) are detectable in most X-linked CMT families. We r eport a novel missense mutation - Tyr65His - in the first extracellular dom ain of the Cx32 gene in a Czech CMTX1 family. The mutation was not detectab le in 50 healthy controls. The clinical phenotype in both the male proband and his mother was moderate with pronounced peroneal weakness and foot drop . Nerve conduction velocities were intermediately decreased (31-38 m/s) in both patients and slowing of central acoustic conduction (BAEP) was found i n both the son and the mother whereas visual central conduction slowing (VE P) was detectable only in the son.