A novel deletion mutation in GJB1 causes X-linked Charcot-Marie-Tooth disease in a Han Chinese family.

X-linked Charcot-Marie-Tooth disease CMT (CMTX) is predominantly caused by mutations in the GJB1 gene that encode connexin32. We describe the clinical findings and the identification of a novel mutation in GJB1 in a large Han Chinese family with CMTX. Linkage to GJB1 was determined by genotyping five polymorphic markers flanking GJB1. Sequence alterations were determined by directly sequencing the coding region of the GJB1 gene. The affected members have variable clinical manifestations. Linkage analysis confirmed the cosegregation of the disease with the GJB1 locus. Sequencing of the GJB1 gene revealed a 1-basepair deletion (c.110delT) in the coding region. The frameshift begins at amino acid 37 and generates a premature stop codon at position 83. The shortened peptide is unlikely to be functional, as it lacks most of the functional domains. The CMTX in this family is caused by a novel loss of function mutation.