A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To report an X-linked dominant Charcot-Marie-Tooth disease (CMTX) Chinese family with vocal cord paresis and to identify the mutation of gap junction protein beta 1 gene (GJB1).</p><p><b>METHODS</b>Part of the family members with dysphagia, dysphonia and lethal respiratory failure were studied through flexible laryngoscope, clinical, brain MRI and electrophysiological examinations. After excluding large fragment tandem duplication containing peripheral myelin protein 22 gene (PMP22), direct sequencing was performed to analyze the mutation of the GJB1 gene in 5 patients including the proband, 5 unaffected family members and 50 unrelated healthy individuals.</p><p><b>RESULTS</b>Eight members spanning 3 generations in this family were affected with CMTX characterized by progressive atrophy and weakness of the anterior tibial and peroneal muscles, especially in the proband. Vocal cord paresis was observed through flexible laryngoscope in total of 4 affected members with dysarthria and dysphagia, 2 of them died of severe respiratory failure due to complete bilateral vocal cord involvement. Normal brain MRI was observed in the proband. The electrophysiological data showed predominant demyelization involving the motor and sensory nerves in the proband. DNA sequencing revealed a de novo c.186 C>G missense mutation in exon 2 of the GJB1 gene, the mutation cosegregated with phenotype.</p><p><b>CONCLUSION</b>Respiratory failure associated with vocal cord involvement may be a rare and severe symptom in CMTX. The present report provides further evidence for clinical and genetic heterogeneity in the X-linked Charcot-Marie-Tooth disease.</p>