A Chinese pedigree with a novel mutation in GJB1 gene and a rare variation in DHTKD1 gene for diverse Charcot‑Marie‑Tooth diseases

Charcot‑Marie‑Tooth (CMT) disease is a group of motor and sensory neuropathies with a high degree of pathological and genetic heterogenicity. The present study described 2 patients with CMT in a Chinese Han pedigree. The proband exhibited the classic manifestation of CMT with slowly progressing muscular atrophy and weakness. Electrophysiological examination highlighted axonal and demyelinating features. His mother did not have any symptoms, but did exhibit abnormal electrophysiological results. Next‑generation sequencing technology was employed to screen mutations in the genes associated with inherited motor never diseases. A novel mutation, c.528_530delAGT, in the gap junction protein beta 1 (GJB1) gene for CMTX, and a rare variation, c.2369C>T, in the dehydrogenase E1 and transketolase domain containing 1 (DHTKD1) gene for CMT disease type 2Q (CMT2Q), were identified in the proband and his mother. The results were verified by Sanger sequencing. Although the in silico analysis predicted no change in the 3‑dimensional structure, the clinical and electrophysiological presentation in the pedigree and the high evolutionary conservation of the affected amino acid supported the hypothesis that the c.528_530delAGT mutation in the GJB1 gene may be pathogenic in this pedigree. In silico analysis and high evolutionary conservation suggested the pathogenicity of the c.2369C>T mutation in the DHTKD1 gene; however, the clinical and electrophysiological performances of the proband and his mother did not conform to those of CMT2Q caused by the DHTKD1 gene. The present study provided additional information concerning the range of mutations of the GJB1 gene, which facilitated the understanding of the genotype‑phenotype association of CMT.