A new mutation in the GJB1 gene of a Chinese family with CMT associated with voc

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Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010 Oct;27(5):497-500.

A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth

disease associated with vocal cord paresis.

Li Q, Liu K, Feng J, Zeng A, Li H, Wu L, Tang Y, Chen M, Lin X, Jiang J.

Department of Neurology, the Affiliated Hospital of Guilin Medical University,

Guilin, Guangxi, 541001 P.R.China.

Abstract

OBJECTIVE: 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).

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.