Genetic Evaluation of Dilated Cardiomyopathy

Papers of particular interest, published recently, have been highlighted as: • Of importance

1. 1.
   Hershberger RE, Morales A, Siegfried JD. Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals. Gen Med. 2010;12:655–67.CrossRefGoogle Scholar
2. 2.
   Harakalova M, van Harssel JJ, Terhal PA, van Lieshout S, Duran K, Renkens I, et al. Dominant missense mutations in ABCC9 cause cantu syndrome. Nat Genet. 2012;44:793–6.PubMedCrossRefGoogle Scholar
3. 3.•
   Lefeber DJ, de Brouwer AP, Morava E, Riemersma M, Schuurs-Hoeijmakers JH, Absmanner B, et al. Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation. PLoS Genet. 2011. DOLK mutations are reported as a cause of primarily non syndromic autosomal recessive DCM in 11 pediatric cases. Google Scholar
4. 4.
   Vasan R, Larson MG, Levy D, Evans JC, Benjamin EJ. Distribution and categorization of echocardiographic measurements in relation to reference limits. The Framingham heart study: formulation of a height- and sex-specific classification and its prospective validation. Circulation. 1997;96:1863–73.PubMedCrossRefGoogle Scholar
5. 5.
   Burkett EL, Hershberger RE. Clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2005;45:969–81.PubMedCrossRefGoogle Scholar
6. 6.
   Mestroni L, Maisch B, McKenna WJ, Schwartz K, Charron P, Rocco C, et al. Guidelines for the study of familial dilated cardiomyopathies. Eur Heart J. 1999;20:93–102.PubMedCrossRefGoogle Scholar
7. 7.
   Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. Eur Heart J. 2008;29:270–6.PubMedCrossRefGoogle Scholar
8. 8.
   Morales A, Pinto JR, Siegfried JD, Li D, Norton N, Hofmeyer M, et al. Late onset sporadic dilated cardiomyopathy caused by a cardiac troponin T mutation. Clin Trans Sci. 2010;3:219–26.CrossRefGoogle Scholar
9. 9.
   Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular noncompaction. J Am Coll Cardiol. 2003;42:2014–27.PubMedCrossRefGoogle Scholar
10. 10.
    Moller DV, Andersen PS, Hedley P, Ersboll MK, Bundgaard H, Moolman-Smook J, et al. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. Eur J Hum Genet. 2009;17:1241–9.PubMedCrossRefGoogle Scholar
11. 11.
    Sen-Chowdhry S, Lowe MD, Sporton SC, McKenna WJ. Arrhythmogenic right ventricular cardiomyopathy: clinical presentation, diagnosis, and management. Am J Med. 2004;117:685–95.PubMedCrossRefGoogle Scholar
12. 12.
    Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D, et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol. 2008;52:2175–87.PubMedCrossRefGoogle Scholar
13. 13.
    Rizzo S, Pilichou K, Thiene G, Basso C. The changing spectrum of arrhythmogenic (right ventricular) cardiomyopathy. Cell Tissue Res. 2012;348:319–23.PubMedCrossRefGoogle Scholar
14. 14.
    Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: an American heart association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention. Circulation. 2006;113:1807–16.PubMedCrossRefGoogle Scholar
15. 15.
    Hershberger RE, Siegfried JD. State of the art review. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2011;57:1641–9.PubMedCrossRefGoogle Scholar
16. 16.
    Sivasankaran S, Sharland GK, Simpson JM. Dilated cardiomyopathy presenting during fetal life. Cardiol Young. 2005;15:409–16.PubMedCrossRefGoogle Scholar
17. 17.
    Rampersaud E et al. Rare variant mutations identified in pediatric patients with dilated cardiomyopathy. Prog Pediatr Cardiol. 2011;31:39–47. Clinical and molecular genetic data from pediatric DCM cases were analyzed, showing that nonsynonymous rare variants, predominantly in sarcomeric genes, are causative of pediatric DCM.PubMedCrossRefGoogle Scholar
18. 18.
    Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the United States: diagnosis, prognosis, and management. J Am Coll Cardiol. 2011;58:659–70.PubMedCrossRefGoogle Scholar
19. 19.
    Rajagopalan N, Attili AK, Bodiwala K, Bailey AL. Features of left ventricular noncompaction in peripartum cardiomyopathy: a case series. Int J Cardiol. 2012.Google Scholar
20. 20.
    Michels M, Hoedemaekers YM, Kofflard MJ, Frohn-Mulder I, Dooijes D, Majoor-Krakauer D, et al. Familial screening and genetic counselling in hypertrophic cardiomyopathy: the Rotterdam experience. Neth Heart J. 2007;15:184–90.PubMedCrossRefGoogle Scholar
21. 21.
    Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familial dilated cardiomyopathy [see comments]. J Am Coll Cardiol. 1998;31:186–94.PubMedCrossRefGoogle Scholar
22. 22.
    Baig MK, Goldman JH, Caforio AP, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll Cardiol. 1998;31:195–201.PubMedCrossRefGoogle Scholar
23. 23.
    Kushner JD, Nauman D, Burgess D, Ludwigsen S, Parks S, Pantely G, et al. Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy. J Cardiac Failure. 2006;12:422–9.CrossRefGoogle Scholar
24. 24.
    Elliott P, O'Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard MN, et al. Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 2010;3:314–22.PubMedCrossRefGoogle Scholar
25. 25.
    Posch MG et al. A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Mol Genet Metab. 2008;95:74–80.PubMedCrossRefGoogle Scholar
26. 26.•
    Garcia-Pavia P, Syrris P, Salas C, Evans A, Mirelis JG, Cobo-Marcos M, et al. Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study. Heart. 2011;97:1744. Mutations in desmosomal genes were identified in patients with advanced DCM, suggesting that the addition of these genes may improve the yield of genetic testing for DCM.PubMedCrossRefGoogle Scholar
27. 27.
    Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004;363:371–2.PubMedCrossRefGoogle Scholar
28. 28.
    Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, et al. X-linked dilated cardiomyopathy. Circulation. 1993;87:1854–65.PubMedCrossRefGoogle Scholar
29. 29.
    Zaragoza MV, Brandon MC, Diegoli M, Arbustini E, Wallace DC. Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny. Eur J Hum Genet. 2011;19:200–7.PubMedCrossRefGoogle Scholar
30. 30.•
    Theis JL, Sharpe KM, Matsumoto ME, Chai HS, Nair AA, Theis JD, et al. Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ Cardiovasc Genet. 2011;4:585–94. Using exome sequencing and homozygosity mapping in a consanguineous family, a homozygous variant in a novel gene associated with autosomal recessive DCM was identified. The gene product, GATA zinc finger domain-containing protein 1, is relevant for gene expression.PubMedCrossRefGoogle Scholar
31. 31.•
    Norton N, Li D, Reider MJ, Siegfried JD, Rampersaud E, Zuchner S, et al. Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. Am J Hum Genet. 2011;88:273–82. Variants in a novel gene, including a large deletion, associated with autosomal dominant, non syndromic DCM are reported for the first time.PubMedCrossRefGoogle Scholar
32. 32.•
    Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, et al. Truncations of titin causing dilated cardiomyopathy. N Engl JMed. 2012;366:619–28. Comprehensive evaluation of TTN suggesting that truncating mutations cause 25% of DCM.CrossRefGoogle Scholar
33. 33.
    Norton N, Robertson PD, Rieder MJ, Zuchner S, Rampersaud E, Martin E, et al. Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the Exome era. Circ Cardiovasc Genet. 2012;5:167–74.PubMedCrossRefGoogle Scholar
34. 34.
    Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, et al. Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol. 2009;65:83–9.PubMedCrossRefGoogle Scholar
35. 35.
    Schonberger J, Wang L, Shin JT, Kim SD, Depreux FF, Zhu H, et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet. 2005;37:418–22.PubMedCrossRefGoogle Scholar
36. 36.
    Gupta P, Bilinska ZT, Sylvius N, Boudreau E, Veinot JP, Labib S, et al. Genetic and ultrastructural studies in dilated cardiomyopathy patients: a large deletion in the lamin A/C gene is associated with cardiomyocyte nuclear envelope disruption. Basic Res Cardiol. 2010;105:365–77.PubMedCrossRefGoogle Scholar
37. 37.
    Norton N, Siegfried JD, Li D, Hershberger RE. Assessment of LMNA copy number variation in 58 probands with dilated cardiomyopathy. Clin Transl Sci. 2011;4:351–2.PubMedCrossRefGoogle Scholar
38. 38.
    Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, et al. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res. 2001;89:1065–72.PubMedCrossRefGoogle Scholar
39. 39.
    Guo W, Bharmal SJ, Esbona K, Greaser ML. Titin diversity—alternative splicing gone wild. J Biomed Biotechnol. 2010;2010:753675.PubMedGoogle Scholar
40. 40.
    Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, et al. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat Med. 2012;18:766–73.PubMedCrossRefGoogle Scholar
41. 41.
    Brauch KM, Karst ML, Herron KJ, de Andrade M, Pellikka PA, Rodeheffer RJ, et al. Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. J Am Coll Cardiol. 2009;54:930–41.PubMedCrossRefGoogle Scholar
42. 42.
    Li D, Morales A, Gonzalez Quintana J, Norton N, Siegfried JD, Hofmeyer M, et al. Identification of novel mutations In RBM20 in patients with dilated cardiomyopathy. Clin Trans Sci. 2010;3:90–7.CrossRefGoogle Scholar
43. 43.
    Gerull B, Gramlich M, Atherton J, McNabb M, Trombitas K, Sasse-Klaassen S, et al. Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet. 2002;14:14.Google Scholar
44. 44.
    Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T, et al. Titin mutations as the molecular basis for dilated cardiomyopathy. Biochem Biophys Res Commun. 2002;291:385–93.PubMedCrossRefGoogle Scholar
45. 45.
    Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, et al. Exome sequencing and genome-wide linkage analysis in 17 families demonstrates the complex contribution of TTN truncating variants to dilated cardiomyopathy. Circ Cardiovasc Genet. 2013;6:144–53.PubMedCrossRefGoogle Scholar
46. 46.
    Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, Jakobs PM, et al. Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clin Transl Sci. 2008;1:21–6.PubMedCrossRefGoogle Scholar
47. 47.
    Hershberger RE, Norton N, Morales A, Li D, Siegfried JD, Gonzalez-Quintana J. Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circ Cardiovasc Genet. 2010;3:155–61.PubMedCrossRefGoogle Scholar
48. 48.
    Hershberger RE, Pinto JR, Parks SB, Kushner JD, Li D, Ludwigsen S, et al. Clinical and functional characterization of TNNT2 mutations identified in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 2009;2:306–13.PubMedCrossRefGoogle Scholar
49. 49.
    Hershberger RE. A glimpse into multigene rare variant genetics: triple mutations in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;55:1454–5.PubMedCrossRefGoogle Scholar
50. 50.
    Kelly M, Semsarian C. Multiple mutations in genetic cardiovascular disease: a marker of disease severity? Circ Cardiovasc Genet. 2009;2:182–90.PubMedCrossRefGoogle Scholar
51. 51.
    Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA. Genetic evaluation of cardiomyopathy—a heart failure society of America practice guideline. J Card Fail. 2009;15:83–97.PubMedCrossRefGoogle Scholar
52. 52.
    Hershberger RE, Cowan J, Morales A, Siegfried JD. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail. 2009;2:253–61.PubMedCrossRefGoogle Scholar
53. 53.•
    Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. 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). Hear Rhythm. 2011;8:1308–39. Recent clinical guidelines highlighting the value of genetic testing for DCM for diagnostic and prognostic purposes in some cases.CrossRefGoogle Scholar
54. 54.•
    Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, et al. Genetic testing for dilated cardiomyopathy in clinical practice. J Card Fail. 2012;18:296–303. Examination of the role of genetic testing for DCM in clinical practice, including a quantification of variants of unknown significance.PubMedCrossRefGoogle Scholar
55. 55.•
    Miller EM, Wang Y, Ware SM. Uptake of cardiac screening and genetic testing among hypertrophic and dilated cardiomyopathy families. J Genet Couns. 2012. Chart review of HCM and DCM cases exploring the implementation of cardiac screening and genetic testing guidelines. Google Scholar
56. 56.
    Genetic information nondiscrimination act (GINA) of 2008. 2010 [cited 2010 December 17]. A brief history of GINA, with information for researchers and health care professionals. ]. Available from: http://www.genome.gov/24519851.
57. 57.•
    Aatre RD, Day SM. Psychological issues in genetic testing for inherited cardiovascular diseases. Circ Cardiovasc Genet. 2011;4:81–90. Discussion of psychosocial issues in cardiovascular genetic counseling, including proposed guidelines for counseling and testing in inherited cardiovascular disease.PubMedCrossRefGoogle Scholar
58. 58.
    Morales A, Cowan J, Dagua J, Hershberger RE. Family history: an essential tool for cardiovascular genetic medicine. Congest Heart Fail. 2008;14:37–45.PubMedCrossRefGoogle Scholar
59. 59.
    Nauman D, Morales A, Cowan J, Dagua J, Hershberger RE. The family history as a tool to identify patients at risk for dilated cardiomyopathy. Prog Cardiovasc Nurs. 2008;23:41–4.PubMedGoogle Scholar