A new mutation in the GJB1 gene of a Chinese family with Charcot-Marie-Tooth disease associated with vocal cord paresis.
- VernacularTitle:伴声带麻痹的X连锁腓骨肌萎缩症GJB1基因新突变
- Author:
Qing-hua LI
1
;
Kai-xiang LIU
;
Jun-lin FENG
;
Ai-yuan ZENG
;
Hao LI
;
Lan WU
;
Yong-gang TANG
;
Mei-lin CHEN
;
Xiao-hui LIN
;
Jing-zi JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Asian Continental Ancestry Group; genetics; Base Sequence; Case-Control Studies; Charcot-Marie-Tooth Disease; genetics; Connexins; genetics; Female; Humans; Male; Molecular Sequence Data; Mutation, Missense; Myelin Proteins; genetics; Pedigree; Vocal Cord Paralysis; genetics; Young Adult
- From: Chinese Journal of Medical Genetics 2010;27(5):497-500
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSPart 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.
RESULTSEight 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.
CONCLUSIONRespiratory 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.