The genetics of hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is most commonly transmitted as an autosomal dominant trait, caused by mutations in genes encoding cardiac sarcomere proteins^1-3. Other inheritable causes of the disease include mutations in genes coding for proteins important in calcium handling or that form part of the cytoskeleton^4-6. At present, the primary clinical role of genetic testing in HCM is to facilitate familial screening to allow the identification of individuals at risk of developing the disease^7,8. It is also used to diagnose genocopies, such as lysosomal^9-11 and glycogen storage disease which have different treatment strategies, rates of disease progression and prognosis^12-14. The role of genetic testing in predicting prognosis is limited at present, but emerging data suggest that knowledge of the genetic basis of disease will assume an important role in disease stratification^15-17 and offer potential targets for disease-modifying therapy in the near future¹⁸.

Figure 1.. Representation of the percentage of hypertrophic cardiomyopathy cases accounted for by pathogenic mutations in sarcomeric and non-sarcomere genes.

Elliott PM, et al; 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC), European Heart Journal 2014; 35 (39): 2733–2779, doi:10.1093/eurheartj/ehu284. Reproduced by permission of Oxford University Press on behalf of the European Society of Cardiology. © European Society of Cardiology 2014. All rights reserved. For permissions please email journals.permissions@oup.com. This figure is not included under the Open Access license of this publication.

Figure 2.. Representation of the cardiac sarcomere with associated proteins and interactions.

Reproduced from Ref. . Abbreviations: TnI, Troponin I; TnC, Troponin C; TnT, Troponin T; Tm, Tropomyosin; c-MYBP-C, cardiac myosin binding protein-c; ELC, Essential Light Chain; RLC, Regulatory Chain; LMM, Light meromyosin. The domains of cMyBP-C are numbered from C0–C10; m is the regulatory motif between domains C1 and C2 and contains the PKA phosphorylation site; PA represents a proline / alanine-rich linker sequence between domains C0 and C1.