期刊
CLINICAL GENETICS
卷 80, 期 3, 页码 256-264出版社
WILEY
DOI: 10.1111/j.1399-0004.2011.01623.x
关键词
ARVC; genetics; immunohistochemistry; TMEM43
资金
- Danish National Arrhythmia Research Foundation Centre for Cardiac Arrhythmia (DARC)
- Danish Cardiovascular Research Academy (DaCRA)
- Research Council at the Heart Centre, Rigshospitalet
- Villadsen Family Foundation
- Brodrene Hartmanns Foundation
- John and Birthe Meyer Foundation
A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed at performing mutational analysis of the gene and characterizing the associated immunohistochemical features. Sixty-five unrelated patients (55 fulfilling Task Force criteria and 10 borderline cases) were screened for mutations in TMEM43. Immunohistochemistry with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c. 1073C>T; in two related patients) and one novel variant (c. 705+7G>A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal level was reduced in all the three TMEM43-positive patients. Immunostaining with plakoglobin-specific antibody also showed reduced signal levels in the three carriers. All patients displayed a similar immunoreactive signal for plakophilin-2, connexin-43, and emerin. In conclusion, two TMEM43 sequence variants were identified in this Danish ARVC cohort. Evaluation of the expression of TMEM43 showed a unique cardiac localization. The immunoreactive signal for the desmosomal protein plakoglobin was reduced in mutation carriers. The TMEM43 gene underlies a distinctive form of ARVC which may share a final common pathway with desmosome-associated ARVC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据