Familial Cardiomyopathies<sup>1</sup>

Biörck, Gunnar; Orinius, E.

doi:10.1111/j.0954-6820.1964.tb00948.x

Cited by 17 publications

(1 citation statement)

References 23 publications

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“…2–4 The pathophysiological mechanisms underlying DCM are heterogeneous, although there has been a longstanding appreciation of a heritable component to DCM. 5, 6 Estimates suggest that up to one third of individuals with DCM have familial disease. 7–11 Indeed, numerous mutations have been identified which are believed to underlie familial DCM.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy

et al. 2012

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BACKGROUND Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous. OBJECTIVES We sought to define the prevalence of mutations in the RNA splicing protein, RBM20, in a large cohort with DCM, and to determine if genetic variation in RBM20 is associated with clinical outcomes. METHODS Subjects included in the GRADE (Genetic Risk Assessment of Defibrillator Events) study were at least 18 years of age, had an ejection fraction of ≤ 30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in DCM subjects; two common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects. RESULTS 1465 subjects were enrolled in the GRADE study and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 ± 13 years, 64% were male and the mean follow up was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in eight subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared to non-mutation carriers. Three of eight subjects (37.5%) with RBM20 mutations had atrial fibrillation (AF) whereas 19 (7.4%) subjects without mutations had AF (p= 0.02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele OR 0.62, 95% CI 0.44–0.86, p=0.006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele OR 0.58, p=0.047). CONCLUSIONS Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers.

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