The val606met mutation in the cardiac beta-myosin heavy chain gene in patients with familial hypertrophic cardiomyopathy is associated with a high risk of sudden death at young age

doi:10.1016/S0002-9149(01)01532-6

The American Journal of Cardiology

Volume 87, Issue 11, 1 June 2001, Pages 1315-1317

https://doi.org/10.1016/S0002-9149(01)01532-6 Get rights and content

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Acknowledgements

We would like to thank H. Petur Nielsen, MD, for his help in obtaining data from Faroe Islands patients.

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The clinical utility of pediatric cardiomyopathy genetic testing: From diagnosis to a precision medicine-based approach to care
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Citation Excerpt :
Multiple studies demonstrate that patients with sarcomere variants tend to be more severely affected than patients with non-sarcomeric variants [30,40]. Within the sarcomere genes, some argue that specific sarcomere variants are inherently more pathogenic than others [41–43]. However, comparing unrelated families with the same variant highlights the marked heterogeneity in disease severity, suggesting other genetic and environmental factors may influence phenotypic expression of disease [41].
Pediatric-onset cardiomyopathies are rare yet cause significant morbidity and mortality in affected children. Genetic testing has a major role in the clinical evaluation of pediatric-onset cardiomyopathies, and identification of a variant in an associated gene can be used to confirm the clinical diagnosis and exclude syndromic causes that may warrant different treatment strategies. Further, risk-predictive testing of first-degree relatives can assess who is at-risk of disease and requires continued clinical follow-up.
In this review, we seek to describe the current role of genetic testing in the clinical diagnosis and management of patients and families with the five major cardiomyopathies. Further, we highlight the ongoing development of precision-based approaches to diagnosis, prognosis, and treatment.
Emerging application of genotype-phenotype correlations opens the door for genetics to guide a precision medicine-based approach to prognosis and potentially for therapies. Despite advances in our understanding of the genetic etiology of cardiomyopathy and increased accessibility of clinical genetic testing, not all pediatric cardiomyopathy patients have a clear genetic explanation for their disease. Expanded genomic studies are needed to understand the cause of disease in these patients, improve variant classification and genotype-driven prognostic predictions, and ultimately develop truly disease-preventing treatment.
Revisiting risk stratification in hypertrophic cardiomyopathy: Do we need to start from scratch?
2012, Heart Rhythm
Familial hypertrophic cardiomyopathy: Basic concepts and future molecular diagnostics
2009, Clinical Biochemistry
Familial hypertrophic cardiomyopathies (FHC) are the most common genetic heart diseases in the United States, affecting nearly 1 in 500 people. Manifesting as increased cardiac wall thickness, this autosomal dominant disease goes mainly unnoticed as most affected individuals are asymptomatic. Up to 1–2% of children and adolescents and 0.5–1% adults with FHC die of sudden cardiac death, making it critical to quickly and accurately diagnose FHC to institute therapy and potentially reduce mortality. However, due to the heterogeneity of the genetic defects in mainly sarcomere proteins, this is a daunting task even with current diagnostic methods. Exciting new methods utilizing high-throughput microarray technology to identify FHC mutations by a method known as array-based resequencing has recently been described. Additionally, next generation sequencing methodologies may aid in improving FHC diagnosis. In this review, we discuss FHC pathophysiology, the rationale for testing, and discuss the limitations and advantages of current and future diagnostics.
The cardiomyopathies
2002, Current Paediatrics
Cardiomyopathies are heart muscle diseases that are classified by pathophysiology: (i) dilated, (ii) hypertrophic, (iii) restrictive. Specific cardiomyopathies are those with a distinct disease association. Most dilated cardiomyopathy in childhood is idiopathic, but specific causes must be excluded as treatment can be directed towards the cause. Dilated cardiomyopathy has a poor prognosis with approximately 60% of children surviving 5 years from presentation. Medical and surgical therapy is improving but ultimately transplantation may be required. Idiopathic hypertrophic cardiomyopathy is a disease of the sarcomere relating to familial defects in genes encoding contractile proteins. Sudden death is common but can be prevented by implanting cardioverter defibrillators in high-risk cases. Restrictive cardiomyopathy is uncommon, it appears more rapidly progressive when presenting in younger patients although the prognosis and molecular genetic causes are not well defined.
Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac β-myosin gene mutations
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^☆: The study was supported by grants from The Danish Heart Foundation; The “Kong Christian den Tiendes Fond”; The Novo Nordisk Foundation; Director Emil C. Hertz and Inger Hertz’s Foundation; Danish Medical Association Research Foundation; and H:S—Copenhagen Hospital Corporation, Copenhagen, Denmark. Manuscript received October 8, 2000; revised manuscript received and accepted December 28, 2000.

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The val606met mutation in the cardiac beta-myosin heavy chain gene in patients with familial hypertrophic cardiomyopathy is associated with a high risk of sudden death at young age☆

Section snippets

Acknowledgements

First page preview

J Mol Cell Cardiol

J Mol Cell Cardiol

Pathology

Biophys J

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy

N Engl J Med

Mutations in the genes for cardiac troponin T and alpha- tropomyosin in hypertrophic cardiomyopathy

N Engl J Med

A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy

Heart

The molecular genetics of hypertrophic cardiomyopathy

Curr Opin Cardiol

Molecular genetic basis of hypertrophic cardiomyopathygenetic markers for sudden cardiac death

J Cardiovasc Electrophysiol

Molecular genetic studies of familial hypertrophic cardiomyopathy

Basic Res Cardiol

The val⁶⁰⁶met mutation in the cardiac beta-myosin heavy chain gene in patients with familial hypertrophic cardiomyopathy is associated with a high risk of sudden death at young age☆