doi: 10.1161/CIRCGENETICS.108.836478
Advances in Genetics, Proteomics, and Metabolomics |
Multiple Mutations in Genetic Cardiovascular Disease
A Marker of Disease Severity?
From the Agnes Ginges Centre for Molecular Cardiology (M.K., C.S.), Centenary Institute, Sydney, Australia; Faculty of Medicine (M.K., C.S.), University of Sydney, Australia; and Department of Cardiology, Royal Prince Alfred Hospital (C.S.), Sydney, Australia.
Correspondence to Christopher Semsarian, MBBS, PhD, Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Locked Bag 6, Newtown, New South Wales 2042, Australia. E-mail c.semsarian@centenary.org.au
Key Words: cardiomyopathy • diagnosis • genetics • genetic heart disease • gene • cardiovascular • multiple mutation • disease severity
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Over the last 2 decades, major advances have been made in our identification and understanding of the genetic basis of cardiovascular disease. More than 40 cardiovascular disorders have now been identified to be directly caused by single-gene defects. These disorders span all aspects of cardiovascular disease and affect all parts of the heart structure. They include the inherited cardiomyopathies such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, and arrhythmogenic right ventricular dysplasia; primary arrhythmogenic disorders such as familial long-QT syndrome (LQTS) and Brugada syndrome; congenital heart diseases such as familial atrial septal defects; vascular diseases such as Marfan syndrome; and metabolic disorders such as familial hypercholesterolemia (FH). Until recently, these cardiac genetic disorders have been thought to involve only single-gene defects (ie, in an individual patient, 1 mutation in a single gene leads to a disease).
Editorial see p 95
A common feature of almost all genetic cardiovascular diseases is the clinical or phenotype heterogeneity observed in the affected individuals both within and between families. Despite harboring the same gene mutation, affected individuals (eg, siblings) can often have marked clinical variability, ranging from no symptoms to severe heart failure and premature death. This widespread clinical heterogeneity suggests other factors apart from the gene mutation itself are important in modifying the clinical phenotype, either by exacerbating or protecting against the disease.1
These modifying factors are poorly understood and may include a number of factors (Figure 1). These include environmental factors such as exercise and diet, age and gender-related influences, and
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