Hypertrophic cardiomyopathy genetics
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Differentiating Hypertrophic Cardiomyopathy from other Diseases |
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Risk calculators and risk factors for Hypertrophic cardiomyopathy genetics |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins.
Mutations
Specific gene mutations that have been identified include the following:
| Gene | Locus | Type |
|---|---|---|
| MYH7 | 14q12 | CMH1 |
| TNNT2 | 1q32 | CMH2 |
| TPM1 | 15q22.1 | CMH3 (115196) |
| MYBPC3 | 11p11.2 | CMH4 (115197) |
| ? | ? | CMH5 |
| PRKAG2 | 7q36 | CMH6 (600858) |
| TNNI3 | 19q13.4 | CMH7 |
| MYL3 | 3p | CMH8 (608751) |
| TTN | 2q24.3 | CMH9 |
| MYL2 | 12q23-q24 | CMH10 |
| ACTC1 | 15q14 | CMH11 (612098) |
| CSRP3 | 11p15.1 | CMH12 (612124) |
About 50-60% of patients with a high index of clinical suspicion for HCM will have a mutation identified in at least 1 of 9 sarcomeric genes. Approximately 45% of these mutations occur in the β myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. Since HCM is typically an autosomal dominant trait, children of an HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk for the disease (HCM Genetic Testing Overview). In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain.
An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes [1] .[2]
References
- ↑ Doolan G, Nguyen L, Chung J, Ingles J, Semsarian C (2004). "Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy". Int J Cardiol. 96 (2): 157–63. doi:10.1016/j.ijcard.2004.05.003. PMID 15314809. Unknown parameter
|month=ignored (help) - ↑ Marian AJ, Yu QT, Workman R, Greve G, Roberts R (1993). "Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death". Lancet. 342 (8879): 1085–6. doi:10.1016/0140-6736(93)92064-Z. PMID 8105312. Unknown parameter
|month=ignored (help)