Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing

Journal of Medical Genetics

Volumn 50, Issue 4, 2013, Pages 228-239

  Lopes, Luis R ^a   Zekavati, Anna ^b   Syrris, Petros ^a   Hubank, Mike ^b   Giambartolomei, Claudia ^a   Dalageorgou, Chrysoula ^a   Jenkins, Sharon ^a   McKenna, William ^a   Plagnol, Vincent ^a   Elliott, Perry M ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA ACTININ 1; ALPHA TROPOMYOSIN; ANKYRIN; CALSEQUESTRIN; CAVEOLIN 2; CONNECTIN; DESMIN; DESMOCOLLIN; DESMOGLEIN 2; DESMOPLAKIN; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR2.1; LAMIN; MYOSIN BINDING PROTEIN C; MYOSIN HEAVY CHAIN; MYOSIN HEAVY CHAIN 6; MYOSIN HEAVY CHAIN 7; MYOSIN LIGHT CHAIN; MYOSIN LIGHT CHAIN 2; MYOSIN LIGHT CHAIN 3; PHOSPHOLAMBAN; PLAKOGLOBIN; PLAKOPHILIN; POTASSIUM CHANNEL KCNE2; POTASSIUM CHANNEL KCNQ1; SODIUM CHANNEL NAV1.5; TRANSFORMING GROWTH FACTOR BETA3; TROPONIN C; TROPONIN I; TROPONIN T; UNCLASSIFIED DRUG; VINCULIN;

ADOLESCENT; ADULT; AGED; ARTICLE; CHILD; CONTROLLED STUDY; EXOME; FEMALE; GENE MUTATION; GENE SEQUENCE; HIGH THROUGHPUT SEQUENCING; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; MAJOR CLINICAL STUDY; MALE; PRESCHOOL CHILD; PRIORITY JOURNAL; SCHOOL CHILD; SINGLE NUCLEOTIDE POLYMORPHISM; UNITED KINGDOM;

ADULT; AMINO ACID SUBSTITUTION; CARDIOMYOPATHY, HYPERTROPHIC; FEMALE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MALE; MIDDLE AGED; MUTATION; PEDIGREE; POLYMORPHISM, SINGLE NUCLEOTIDE; SARCOMERES;

EID: 84878823562     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2012-101270     Document Type: Article

References (92)

1. Elliott P, McKenna WJ. Hypertrophic cardiomyopathy. Lancet 2004;363:1881-91.
2. Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH III, Spirito P, Ten Cate FJ, Wigle ED. American college of cardiology/european society of cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the american college of cardiology foundation task force on clinical expert consensus documents and the european society of cardiology committee for practice guidelines. J Am Coll Cardiol 2003;42:1687-713.
3. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. 2011 accf/aha guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. Developed in collaboration with the american association for thoracic surgery, american society of echocardiography, american society of nuclear cardiology, heart failure society of america, heart rhythm society, society for cardiovascular angiography and interventions, and society of thoracic surgeons. J Am Coll Cardiol 2011;58:e212-60.
4. Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, Mahon NG, McKenna WJ. Sudden death in hypertrophic cardiomyopathy: identification of high risk patients. J Am Coll Cardiol 2000;36:2212-18.
5. Elliott PM, Gimeno Blanes JR, Mahon NG, Poloniecki JD, McKenna WJ. Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 2001;357:420-4.
6. Elliott PM, Gimeno JR, Thaman R, Shah J, Ward D, Dickie S, Tome Esteban MT, McKenna WJ. Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy. Heart 2006;92:785-91.
7. Marian AJ, Roberts R. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol 2001;33:655-70.
8. Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE. Shared genetic causes of cardiac hypertrophy in children and adults. N Engl J Med 2008;358:1899-908.
9. Van Driest SL, Ommen SR, Tajik AJ, Gersh BJ, Ackerman MJ. Yield of genetic testing in hypertrophic cardiomyopathy. Mayo Clin Proc 2005;80:739-44.
10. Millat G, Bouvagnet P, Chevalier P, Dauphin C, Jouk PS, Da Costa A, Prieur F, Bresson JL, Faivre L, Eicher JC, Chassaing N, Crehalet H, Porcher R, Rodriguez-Lafrasse C, Rousson R. Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. Eur J Med Genet 2010;53:261-7.
11. 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.
12. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell 1990;62:999-1006.
13. Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE. Mutations in the cardiac myosin binding protein-c gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet 1995;11:434-7.
14. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE. Alpha-tropomyosin and cardiac troponin t mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell 1994;77:701-12.
15. Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet 1996;13:63-9.
16. Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A, Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H, Koga Y, Imaizumi T, Sasazuki T. Mutations in the cardiac troponin i gene associated with hypertrophic cardiomyopathy. Nat Genet 1997;16:379-82.
17. Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression. Nat Clin Pract Cardiovasc Med 2008;5:158-68.
18. Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P, Helio T, Keren A, McKenna WJ, Monserrat L, Pankuweit S, Perrot A, Rapezzi C, Ristic A, Seggewiss H, van Langen I, Tavazzi L. Genetic counselling and testing in cardiomyopathies: a position statement of the european society of cardiology working group on myocardial and pericardial diseases. Eur Heart J 2010;31:2715-26.
19. 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.
20. Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet 2010;11:31-46.
21. McKenna WJ, Spirito P, Desnos M, Dubourg O, Komajda M. Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart 1997;77:130-2.
22. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. The sequence alignment/map format and samtools. Bioinformatics 2009;25:2078-9.
23. Wang K, Li M, Hakonarson H. Annovar: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38:e164.
24. 1000 Genomes Project Consortium A map of human genome variation from population-scale sequencing. Nature 2010;467:1061-73.
25. Smigielski EM, Sirotkin K, Ward M, Sherry ST. Dbsnp: a database of single nucleotide polymorphisms. Nucleic Acids Res 2000;28:352-5.
26. Ng PC, Henikoff S. Sift: predicting amino acid changes that affect protein function. Nucleic Acids Res 2003;31:3812-14.
27. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Methods 2010;7:248-9.
28. Brito D, Madeira H. Malignant mutations in hypertrophic cardiomyopathy: fact or fancy. Rev Port Cardiol 2005;24:1137-46.
29. 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.
30. Niimura H, Patton KK, McKenna WJ, Soults J, Maron BJ, Seidman JG, Seidman CE. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 2002;105:446-51.
31. Morner S, Richard P, Kazzam E, Hellman U, Hainque B, Schwartz K, Waldenstrom A. Identification of the genotypes causing hypertrophic cardiomyopathy in northern sweden. J Mol Cell Cardiol 2003;35:841-9.
32. Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ. Myosin binding protein c mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol 2004;44:1903-10.
33. Girolami F, Olivotto I, Passerini I, Zachara E, Nistri S, Re F, Fantini S, Baldini K, Torricelli F, Cecchi F. A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein c and troponin t genes in italian patients with hypertrophic cardiomyopathy. J Cardiovasc Med (Hagerstown) 2006;7:601-7.
34. 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.
35. Zimmerman RS, Cox S, Lakdawala NK, Cirino A, Mancini-DiNardo D, Clark E, Leon A, Duffy E, White E, Baxter S, Alaamery M, Farwell L, Weiss S, Seidman CE, Seidman JG, Ho CY, Rehm HL, Funke BH. A novel custom resequencing array for dilated cardiomyopathy. Genet Med 2010;12:268-78.
36. Millat G, Chanavat V, Crehalet H, Rousson R. Development of a high resolution melting method for the detection of genetic variations in hypertrophic cardiomyopathy. Clin Chim Acta 2010;411:1983-91.
37. Nanni L, Pieroni M, Chimenti C, Simionati B, Zimbello R, Maseri A, Frustaci A, Lanfranchi G. Hypertrophic cardiomyopathy: two homozygous cases with "Typical" Hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy. Biochem Biophys Res Commun 2003;309:391-8.
38. Konno T, Shimizu M, Ino H, Matsuyama T, Yamaguchi M, Terai H, Hayashi K, Mabuchi T, Kiyama M, Sakata K, Hayashi T, Inoue M, Kaneda T, Mabuchi H. A novel missense mutation in the myosin binding protein-c gene is responsible for hypertrophic cardiomyopathy with left ventricular dysfunction and dilation in elderly patients. J Am Coll Cardiol 2003;41:781-6.
39. Watkins H, McKenna WJ, Thierfelder L, Suk HJ, Anan R, O'Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG, Seidman C. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med 1995;332:1058-64.
40. Moolman JC, Corfield VA, Posen B, Ngumbela K, Seidman C, Brink PA, Watkins H. Sudden death due to troponin t mutations. J Am Coll Cardiol 1997;29:549-55.
41. Yamauchi-Takihara K, Nakajima-Taniguchi C, Matsui H, Fujio Y, Kunisada K, Nagata S, Kishimoto T. Clinical implications of hypertrophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene. Heart 1996;76:63-5.
42. Morita H, Larson MG, Barr SC, Vasan RS, O'Donnell CJ, Hirschhorn JN, Levy D, Corey D, Seidman CE, Seidman JG, Benjamin EJ. Single-gene mutations and increased left ventricular wall thickness in the community: the framingham heart study. Circulation 2006;113:2697-705.
43. Alpert NR, Mohiddin SA, Tripodi D, Jacobson-Hatzell J, Vaughn-Whitley K, Brosseau C, Warshaw DM, Fananapazir L. Molecular and phenotypic effects of heterozygous, homozygous, and compound heterozygote myosin heavy-chain mutations. Am J Physiol Heart Circ Physiol 2005;288:H1097-102.
44. 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.
45. Gruver EJ, Fatkin D, Dodds GA, Kisslo J, Maron BJ, Seidman JG, Seidman CE. Familial hypertrophic cardiomyopathy and atrial fibrillation caused by arg663his beta-cardiac myosin heavy chain mutation. Am J Cardiol 1999;83:13H-18H.
46. Kaski JP, Syrris P, Esteban MT, Jenkins S, Pantazis A, Deanfield JE, McKenna WJ, Elliott PM. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. Circ Cardiovasc Genet 2009;2:436-41.
47. Fananapazir L, Dalakas MC, Cyran F, Cohn G, Epstein ND. Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. Proc Natl Acad Sci USA 1993;90:3993-7.
48. Woo A, Rakowski H, Liew JC, Zhao MS, Liew CC, Parker TG, Zeller M, Wigle ED, Sole MJ. Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart 2003;89:1179-85.
49. Erdmann J, Daehmlow S, Wischke S, Senyuva M, Werner U, Raible J, Tanis N, Dyachenko S, Hummel M, Hetzer R, Regitz-Zagrosek V. Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. Clin Genet 2003;64:339-49.
50. Consevage MW, Salada GC, Baylen BG, Ladda RL, Rogan PK. A new missense mutation, arg719gln, in the beta-cardiac heavy chain myosin gene of patients with familial hypertrophic cardiomyopathy. Hum Mol Genet 1994;3:1025-6.
51. Mohiddin SA, Begley DA, McLam E, Cardoso JP, Winkler JB, Sellers JR, Fananapazir L. Utility of genetic screening in hypertrophic cardiomyopathy: prevalence and significance of novel and double (homozygous and heterozygous) beta-myosin mutations. Genet Test 2003;7:21-7.
52. Bos JM, Poley RN, Ny M, Tester DJ, Xu X, Vatta M, Towbin JA, Gersh BJ, Ommen SR, Ackerman MJ. Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle lim protein, and telethonin. Mol Genet Metab 2006;88:78-85.
53. Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin i mutations. J Clin Invest 2003;111:209-16.
54. Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA, Dudley SC, Shalaby AA, Weiss R, McNamara DM, London B, Ellinor PT. Genetic variation in the alternative splicing regulator rbm20 is associated with dilated cardiomyopathy. Heart Rhythm 2012;9:390-6.
55. Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR. The cardiac mechanical stretch sensor machinery involves a z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 2002;111:943-55.
56. Charron P, Dubourg O, Desnos M, Bennaceur M, Carrier L, Camproux AC, Isnard R, Hagege A, Langlard JM, Bonne G, Richard P, Hainque B, Bouhour JB, Schwartz K, Komajda M. Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein c gene. Circulation 1998;97:2230-6.
57. Lakdawala NK, Thune JJ, Maron BJ, Cirino AL, Havndrup O, Bundgaard H, Christiansen M, Carlsen CM, Dorval JF, Kwong RY, Colan SD, Kober LV, Ho CY. Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy. Am J Cardiol 2011;108:1606-13.
58. 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.
59. Laredo R, Monserrat L, Hermida-Prieto M, Fernandez X, Rodriguez I, Cazon L, Alvarino I, Dumont C, Pinon P, Peteiro J, Bouzas B, Castro-Beiras A. [beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy]. Rev Esp Cardiol 2006;59:1008-18.
60. Ohsuzu F, Katsushika S, Akanuma M, Nakamura H, Harada H, Satoh M, Hiroi S, Kimura A. Hypertrophic obstructive cardiomyopathy due to a novel t-to-a transition at codon 624 in the beta-myosin heavy chain (beta-mhc) gene possibly related to the sudden death. Int J Cardiol 1997;62:203-9.
61. Olivotto I, Girolami F, Ackerman MJ, Nistri S, Bos JM, Zachara E, Ommen SR, Theis JL, Vaubel RA, Re F, Armentano C, Poggesi C, Torricelli F, Cecchi F. Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clin Proc 2008;83:630-8.
62. Waldmuller S, Muller M, Rackebrandt K, Binner P, Poths S, Bonin M, Scheffold T. Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy. Clin Chem 2008;54:682-7.
63. Gimeno JR, Monserrat L, Perez-Sanchez I, Marin F, Caballero L, Hermida-Prieto M, Castro A, Valdes M. Hypertrophic cardiomyopathy. A study of the troponin-t gene in 127 spanish families. Rev Esp Cardiol 2009;62:1473-7.
64. Posch MG, Waldmuller S, Muller M, Scheffold T, Fournier D, Andrade-Navarro MA, De Geeter B, Guillaumont S, Dauphin C, Yousseff D, Schmitt KR, Perrot A, Berger F, Hetzer R, Bouvagnet P, Ozcelik C. Cardiac alpha-myosin (myh6) is the predominant sarcomeric disease gene for familial atrial septal defects. PLoS One 2011;6:e28872.
65. Arimura T, Bos JM, Sato A, Kubo T, Okamoto H, Nishi H, Harada H, Koga Y, Moulik M, Doi YL, Towbin JA, Ackerman MJ, Kimura A. Cardiac ankyrin repeat protein gene (ankrd1) mutations in hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:334-42.
66. Quarta G, Muir A, Pantazis A, Syrris P, Gehmlich K, Garcia-Pavia P, Ward D, Sen-Chowdhry S, Elliott PM, McKenna WJ. Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. Circulation 2011;123:2701-9.
67. Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H. De novo desmin-mutation n116s is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet 2010;19:4595-607.
68. Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C, Frank R, Hainque B, Charron P. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace 2010;12:861-8.
69. Basso C, Czarnowska E, Della Barbera M, Bauce B, Beffagna G, Wlodarska EK, Pilichou K, Ramondo A, Lorenzon A, Wozniek O, Corrado D, Daliento L, Danieli GA, Valente M, Nava A, Thiene G, Rampazzo A. Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur Heart J 2006;27:1847-54.
70. van der Zwaag PA, Jongbloed JD, van den Berg MP, van der Smagt JJ, Jongbloed R, Bikker H, Hofstra RM, van Tintelen JP. A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy. Hum Mutat 2009;30:1278-83.
71. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, Hofman N, Bikker H, van Tintelen JP, Mannens MM, Wilde AA, Ackerman MJ. The ryr2-encoded ryanodine receptor/ calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long qt syndrome: a comprehensive open reading frame mutational analysis. J Am Coll Cardiol 2009;54:2065-74.
72. Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, Driskell IM, Schott JJ, Norris K, Leenhardt A, Kim RB, Escande D, Roden DM. Defining the cellular phenotype of "Ankyrin-b syndrome" Variants: human ank2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation 2007;115:432-41.
73. Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, Priori SG, Keating MT, Bennett V. A cardiac arrhythmia syndrome caused by loss of ankyrin-b function. Proc Natl Acad Sci USA 2004;101:9137-42.
74. Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH. Sodium channel abnormalities are infrequent in patients with long qt syndrome: identification of two novel scn5a mutations. Am J Med Genet 1999;86:470-6.
75. Sherman J, Tester DJ, Ackerman MJ. Targeted mutational analysis of ankyrin-b in 541 consecutive, unrelated patients referred for long qt syndrome genetic testing and 200 healthy subjects. Heart Rhythm 2005;2:1218-23.
76. Cronk LB, Ye B, Kaku T, Tester DJ, Vatta M, Makielski JC, Ackerman MJ. Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. Heart Rhythm 2007;4:161-6.
77. Garcia-Pavia P, Syrris P, Salas C, Evans A, Mirelis JG, Cobo-Marcos M, Vilches C, Bornstein B, Segovia J, Alonso-Pulpon L, Elliott PM. Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study. Heart 2011;97:1744-52.
78. den Haan AD, Tan BY, Zikusoka MN, Llado LI, Jain R, Daly A, Tichnell C, James C, Amat-Alarcon N, Abraham T, Russell SD, Bluemke DA, Calkins H, Dalal D, Judge DP. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet 2009;2:428-35.
79. Kapplinger JD, Landstrom AP, Salisbury BA, Callis TE, Pollevick GD, Tester DJ, Cox MG, Bhuiyan Z, Bikker H, Wiesfeld AC, Hauer RN, van Tintelen JP, Jongbloed JD, Calkins H, Judge DP, Wilde AA, Ackerman MJ. Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise. J Am Coll Cardiol 2011;57:2317-27.
80. Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ. Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease. Eur Heart J 2007;28:581-8.
81. Millat G, Chevalier P, Restier-Miron L, Da Costa A, Bouvagnet P, Kugener B, Fayol L, Gonzalez Armengod C, Oddou B, Chanavat V, Froidefond E, Perraudin R, Rousson R, Rodriguez-Lafrasse C. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long qt syndrome. Clin Genet 2006;70:214-27.
82. Norton N, Robertson PD, Rieder MJ, Zuchner S, Rampersaud E, Martin E, Li D, Nickerson DA, Hershberger RE. Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. Circ Cardiovasc Genet 2012;5:167-74.
83. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol 2009;54:201-11.
84. Page SP, Kounas S, Syrris P, Christiansen M, Frank-Hansen R, Anderson PS, Elliott PM, McKenna WJ. Cardiac myosin binding protein-c mutations in families 1396 with hypertrophic cardiomyopathy: disease expression in relation to age, gender, 1397 and long term outcome. Circ Cardiovasc Genet 2012. 5(2):156-66
85. Pasquale F, Syrris P, Kaski JP, Mogensen J, McKenna WJ, Elliott P. Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin t gene. Circ Cardiovasc Genet 2012;5:10-17.
86. Carniel E, Taylor MR, Sinagra G, Di Lenarda A, Ku L, Fain PR, Boucek MM, Cavanaugh J, Miocic S, Slavov D, Graw SL, Feiger J, Zhu XZ, Dao D, Ferguson DA, Bristow MR, Mestroni L. Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy. Circulation 2005;112:54-9.
87. Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C, Magnusson OT, Helgason A, Saemundsdottir J, Gylfason A, Stefansdottir H, Gretarsdottir S, Matthiasson SE, Thorgeirsson GM, Jonasdottir A, Sigurdsson A, Stefansson H, Werge T, Rafnar T, Kiemeney LA, Parvez B, Muhammad R, Roden DM, Darbar D, Thorleifsson G, Walters GB, Kong A, Thorsteinsdottir U, Arnar DO, Stefansson K. A rare variant in myh6 is associated with high risk of sick sinus syndrome. Nat Genet 2011;43:316-20.
88. LeWinter MM, Granzier H. Cardiac titin: a multifunctional giant. Circulation 2010;121:2137-45.
89. Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJ, Cook SA, Mestroni L, Seidman JG, Seidman CE. Truncations of titin causing dilated cardiomyopathy. N Engl J Med 2012;366: 619-28.
90. Gautel M. The sarcomeric cytoskeleton: who picks up the strain. Curr Opin Cell Biol 2011;23:39-46.
91. Sen-Chowdhry S, Morgan RD, Chambers JC, McKenna WJ. Arrhythmogenic cardiomyopathy: Etiology, diagnosis, and treatment. Annu Rev Med 2010;61:233-53.
92. Elliott P, O'Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard MN, Carr-White G, Pantazis A, McKenna WJ. Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy. Circ Cardiovasc Genet 2010;3:314-22.