Background Mutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with an identical mutation. Such clinical variation is often thought to be explained largely by differences in genetic background or ‘modifier genes’. We aimed to test the prediction that identical genetic backgrounds result in largely similar clinical expression of a cardiac disease causing mutation, by studying the clinical expression of mutations causing cardiac disease in monozygotic twins.
Methods We compared first available clinical information on 46 monozygotic twin pairs and 59 control pairs that had either a hereditary cardiomyopathy or channelopathy.
Results Despite limited power of this study, we found significant heritability for corrected QT interval (QTc) in long QT syndrome (LQTS). We could not detect significant heritability for structural traits, but found a significant environmental effect on thickness of the interventricular septum in hypertrophic cardiomyopathy.
Conclusions Our study confirms previously found robust heritability for electrical traits like QTc in LQTS, and adds information on low or lacking heritability for structural traits in heritable cardiomyopathies. This may steer the search for genetic modifiers in heritable cardiac disease.
- Twin Study
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Contributors Planning: JJ, KYvS-Z, AW, YMP. Conduct: JJ, KYvS-Z, MWTT, JPvT, IC, JvdS, AV, JMB, AJM, HS, SP, BT, PR, AR, UBD, JT-H, MA, IO, PC, JRG, EJWR, MvdB, AW, YMP. Reporting: JJ, KYvS-Z, MWTT, JPvT, MA, AW, YMP. Overall: JJ, KYvS-Z, YMP.
Funding This work was supported by the Netherlands CardioVascular Research Initiative (Project PREDICT and ARENA): the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development, the Royal Netherlands Academy of Sciences, the Windland Smith Rice Comprehensive Sudden Cardiac Death Program, the Finnish Foundation for Cardiovascular Research and the Novo Nordic Foundation.
Competing interests MA is a consultant for Boston Scientific, Gilead Sciences, Medtronic and St. Jude Medical. MA and Mayo Clinic received sales-based royalties from Transgenomic for their FAMILION-LQTS and FAMILION-CPVT genetic tests. However, these entities had no involvement with this study. The remaining authors have nothing to disclose.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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