Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8279294 | Journal of the Neurological Sciences | 2013 | 5 Pages |
Abstract
Mutations in the 5â² non-coding region of GJB1 are rarely reported in patients with Charcot-Marie-Tooth disease (CMT). We therefore aimed to assess the frequency and identities of the GJB1 5â² non-coding region mutations in a cohort of CMT. We analyzed the 5â² non-coding region of GJB1 (including the promoter P2 and exon 1b) in 91 unrelated CMT patients without an identified genetic cause. Two mutations, c.-529T>C, and c.-459C>T, were identified in one patient each. One polymorphism, c.-713G>A, was also identified in 53 patients and 73 of the 100 control subjects. The luciferase reporter assays showed that c.-459C>T significantly reduced the luciferase expression with or without SOX10 activation, whereas c.-529T>C impaired the expression only with SOX10 co-expression. c.-713G>A had no apparent functional effect. Mutations in the 5â² non-coding region of GJB1 account for 0.8% (2 of 251) of CMT and 2.2% (2 of 91) of genetically unassigned CMT in a Taiwanese cohort. As previously demonstrated, c.-459C>T and c.-529T>C may cause CMT through compromising GJB1 expression whereas c.-713G>A is a benign variant. This study highlights the pathogenic role of the GJB1 5â² non-coding region mutations in CMT, and suggests that their identification should be considered for CMT patients without commonly observed mutations.
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Authors
Pei-Chien Tsai, Chung-Huang Chen, An-Bon Liu, Yun-Chung Chen, Bing-Wen Soong, Kon-Ping Lin, Shaw-Fang Yet, Yi-Chung Lee,