Abstract
Since 1989, major advances have been made in our understanding of the genetic basis of HCM. Our genetic advances have led to a complete re-definition of HCM as a complex medical genetic disorder of the sarcomere. To date, over 1,300 mutations in at least 13 disease genes have been identified in patients with HCM. This genetic information has had its greatest impact in the setting of predictive testing in at-risk family members. The genetic testing process in HCM requires a multidisciplinary approach, which includes the cardiologist, genetic counselor, geneticists, and patient support groups. Careful phenotyping of HCM patients, comprehensive pre- and post- test genetic counseling, careful interpretation of the genetic reports, and systematic application of the genetic result in the setting of the HCM family are all key components of care. The latest genetic technologies, including whole genome sequencing, will likely translate to a greater understanding of the genetic and molecular underpinnings of HCM.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20:1–8.
Seidman J, Seidman C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell. 2001;104:557–67.
Nabel EG. Cardiovascular disease. N Engl J Med. 2003;349:60–72.
Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60:705–15.
Ingles J, Sarina T, Yeates L, Hunt L, Macciocca I, McCormack L, Winship I, McGaughran J, Atherton J, Semsarian C. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy. Genet Med. 2013;15(12):972–7.
Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992;326:1108–14.
Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, Kristinsson A, Roberts R, Sole M, Maron BJ, Seidman JG, Seidman CE. Mutations in the gene for cardiac myosin-binding protein c and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998;338:1248–57.
Semsarian C, Yu B, Ryce C, Lawrence C, Washington H, Trent RJ. Sudden cardiac death in familial hypertrophic cardiomyopathy: are “benign” mutations really benign? Pathology. 1997;29:305–8.
Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8:1308–39.
Ingles J, Yeates L, Semsarian C. The emerging role of the cardiac genetic counselor. Heart Rhythm. 2011;8:1958–62.
Das KJ, Ingles J, Bagnall RD, Semsarian C. Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment. Genet Med. 2013;16(4):286–93.
Ingles J, McGaughran J, Scuffham PA, Atherton J, Semsarian C. A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy. Heart. 2012;98(8):625–30.
Maron BJ, Semsarian C. Emergence of gene mutation carriers and the expanding disease spectrum of hypertrophic cardiomyopathy. Eur Heart J. 2010;31:1551–3.
Maron BJ, Yeates L, Semsarian C. Clinical challenges of genotype positive (+)-phenotype negative (−) family members in hypertrophic cardiomyopathy. Am J Cardiol. 2011;107:604–8.
Gray B, Ingles J, Semsarian C. Natural history of genotype positive-phenotype negative patients with hypertrophic cardiomyopathy. Int J Cardiol. 2011;152:258–9.
Kelly M, Semsarian C. Multiple mutations in genetic cardiovascular disease: a marker of disease severity? Circ Cardiovasc Genet. 2009;2:182–90.
Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: Implications for genetic testing and counselling. J Med Genet. 2005;42:e59.
Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003;107:2227–32.
Maron BJ, Maron MS, Semsarian C. Double or compound sarcomere mutations in hypertrophic cardiomyopathy: a potential link to sudden death in the absence of conventional risk factors. Heart Rhythm. 2012;9:57–63.
Ingles J, Semsarian C. Sudden cardiac death in the young: a clinical genetic approach. Intern Med J. 2007;37:32–7.
Ingles J, Lind JM, Phongsavan P, Semsarian C. Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy. Genet Med. 2008;10:117–20.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer-Verlag London
About this chapter
Cite this chapter
Semsarian, C., Ingles, J. (2015). Genetics of HCM and Role of Genetic Testing. In: Naidu, S. (eds) Hypertrophic Cardiomyopathy. Springer, London. https://doi.org/10.1007/978-1-4471-4956-9_6
Download citation
DOI: https://doi.org/10.1007/978-1-4471-4956-9_6
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-4955-2
Online ISBN: 978-1-4471-4956-9
eBook Packages: MedicineMedicine (R0)