期刊
HEART RHYTHM
卷 8, 期 8, 页码 1214-1221出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2011.03.015
关键词
Arrhythmia; Arrhythmogenic right ventricular cardiomyopathy; Cell adhesion; Desmosome; Genetics
资金
- Academy of Finland [129494]
- Sigrid Juselius Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Cultural Foundation
- Emil Aaltonen Foundation
- Finnish Medical Foundation
- Aarne Koskelo Foundation
- special governmental subsidy for health sciences research
- Academy of Finland (AKA) [129494, 129494] Funding Source: Academy of Finland (AKA)
BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive myocardial disorder caused by mutations of desmosomal cell adhesion proteins. The prevalence of these variants in the general population is unknown. OBJECTIVE This study examined the spectrum and population prevalence of desmosomal mutations predisposing to ARVC in Finland. METHODS We screened 29 Finnish ARVC probands for mutations in the DSP, DSG2, and DSC2 genes. All Finnish-type ARVC-associated mutations, including those 3 previously identified in PKP2 in the same patient group, were analyzed in the population-based Health 2000 cohort of 6,334 individuals and tested for association with electrocardiographic variables. RESULTS We detected 2 novel mutations: DSG2 3059_3062delAGAG and DSP T1373A. DSG2 3059_3062delAGAG was present in a family with 5 mutation carriers. The endomyocardial samples of the DSG2 deletion carrier showed reduced immunoreactive signal for desmoglein-2, plakophilin-2, plakoglobin, and desmoplakin. DSP T1373A was found in 1 proband with typical right ventricular disease and exercise-related ventricular tachycardia. In the population sample, the collective prevalence of all 5 mutations identified in the 29 ARVC patients (PKP2 Q62K, Q59L, N613K, DSG2 3059_3062delAGAG, and DSP T1373A) was 31 of 6,334 individuals, or 0.5%. The apparent founder mutation PKP2 Q59L is present in 0.3% of Finns and was previously shown to have an approximately 20% disease penetrance. CONCLUSION One of 200 Finns carries a desmosomal mutation that may predispose to ARVC and its clinical sequelae. ARVC-associated mutations may thus be more prevalent in the population than expected based on the published ARVC prevalence data.
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