Importance of Variant Interpretation in Whole-Exome Molecular Autopsy: Population-Based Case Series

Circulation

Volumn 137, Issue 25, 2018, Pages 2705-2715

  Shanks, Garrett W ^a   Tester, David J ^a   Ackerman, Jaeger P ^a   Simpson, Michael A ^c   Behr, Elijah R ^d,e   White, Steven M ^f,g   Ackerman, Michael J ^a,b  

^a MAYO GRADUATE SCHOOL   (United States)

^b MAYO CLINIC   (United States)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^e ST GEORGE'S UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^f Office of the Medical Examiner   (United States)

^g NORTHWESTERN UNIVERSITY   (United States)

Author keywords

cardiomyopathies; channelopathies; genetics; sudden death

Indexed keywords

SODIUM CHANNEL NAV1.5;

ADOLESCENT; ADULT; AMINO ACID SUBSTITUTION; ARTICLE; AUTOPSY; BLACK PERSON; CARDIOMYOPATHY; CASE STUDY; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CAUCASIAN; CHILD; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DES GENE; FEMALE; FRAMESHIFT MUTATION; GENE; GENETIC SCREENING; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; ILLINOIS; INFANT; MALE; MEDICALLY UNEXPLAINED SYMPTOM; MYH7 GENE; PATHOGENICITY; PREVALENCE; PRIORITY JOURNAL; RYR2 GENE; SCN5A GENE; SUDDEN CARDIAC DEATH; TTN GENE; WHOLE EXOME SEQUENCING; YOUNG ADULT; CAUSE OF DEATH; CHANNELOPATHY; GENETIC PREDISPOSITION; GENETICS; MOLECULAR PATHOLOGY; MORTALITY; PATHOLOGY; PHENOTYPE; PREDICTIVE VALUE; PROCEDURES; REPRODUCIBILITY; RISK FACTOR;

ADOLESCENT; ADULT; AUTOPSY; CAUSE OF DEATH; CHANNELOPATHIES; DEATH, SUDDEN, CARDIAC; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; ILLINOIS; MALE; PATHOLOGY, MOLECULAR; PHENOTYPE; PREDICTIVE VALUE OF TESTS; REPRODUCIBILITY OF RESULTS; RISK FACTORS; WHOLE EXOME SEQUENCING; YOUNG ADULT;

EID: 85059904372     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.117.031053     Document Type: Article

References (33)

1. Kong MH, Fonarow GC, Peterson ED, Curtis AB, Hernandez AF, Sanders GD, Thomas KL, Hayes DL, Al-Khatib SM. Systematic review of the incidence of sudden cardiac death in the united states. J Am Coll Cardiol. 2011; 57: 794-801. doi: 10.1016/j.jacc.2010.09.064.
2. Mehra R. Global public health problem of sudden cardiac death. J Electrocardiol. 2007; 40(6 Suppl): S118-S122. doi: 10.1016/j.jelectrocard.2007.06.023.
3. Virmani R, Burke AP, Farb A. Sudden cardiac death. Cardiovasc Pathol. 2001; 10: 275-282.
4. Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep. 2008; 56: 1-120.
5. Bagnall RD, Weintraub RG, Ingles J, Duflou J, Yeates L, Lam L, Davis AM, Thompson T, Connell V, Wallace J, Naylor C, Crawford J, Love DR, Hallam L, White J, Lawrence C, Lynch M, Morgan N, James P, du Sart D, Puranik R, Langlois N, Vohra J, Winship I, Atherton J, McGaughran J, Skinner JR, Semsarian C. A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016; 374: 2441-2452. doi: 10.1056/NEJMoa1510687.
6. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013; 10: 1932-1963. doi: 10.1016/j.hrthm.2013.05.014.
7. 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; Heart Rhythm Society (HRS); European Heart Rhythm Association (EHRA). 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). Europace. 2011; 13: 1077-1109. doi: 10.1093/europace/eur245.
8. Skinner JR, Duflou JA, Semsarian C. Reducing sudden death in young people in Australia and New Zealand: the TRAGADY initiative. Med J Aust. 2008; 189: 539-540.
9. Anderson JH, Tester DJ, Will ML, Ackerman MJ. Whole-exome molecular autopsy after exertion-related sudden unexplained death in the young. Circ Cardiovasc Genet. 2016; 9: 259-265. doi: 10.1161/CIRCGENETICS.115.001370.
10. Bagnall RD, Das K J, Duflou J, Semsarian C. Exome analysis-based molecular autopsy in cases of sudden unexplained death in the young. Heart Rhythm. 2014; 11: 655-662. doi: 10.1016/j.hrthm.2014.01.017.
11. Christiansen SL, Hertz CL, Ferrero-Miliani L, Dahl M, Weeke PE, Lu-Camp, Ottesen GL, Frank-Hansen R, Bundgaard H, Morling N. Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting. Eur J Hum Genet. 2016; 24: 1797-1802. doi: 10.1038/ejhg.2016.118.
12. Loporcaro CG, Tester DJ, Maleszewski JJ, Kruisselbrink T, Ackerman MJ. Confirmation of cause and manner of death via a comprehensive cardiac autopsy including whole exome next-generation sequencing. Arch Pathol Lab Med. 2014; 138: 1083-1089. doi: 10.5858/arpa.2013-0479-SA.
13. Narula N, Tester DJ, Paulmichl A, Maleszewski JJ, Ackerman MJ. Postmortem whole exome sequencing with gene-specific analysis for autopsynegative sudden unexplained death in the young: a case series. Pediatr Cardiol. 2015; 36: 768-778. doi: 10.1007/s00246-014-1082-4.
14. Santori M, Blanco-Verea A, Gil R, Cortis J, Becker K, Schneider PM, Carracedo A, Brion M. Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood. Arch Dis Child. 2015; 100: 952-956. doi: 10.1136/archdischild-2015-308200.
15. Lahrouchi N, Raju H, Lodder EM, Papatheodorou E, Ware JS, Papadakis M, Tadros R, Cole D, Skinner JR, Crawford J, Love DR, Pua CJ, Soh BY, Bhalshankar JD, Govind R, Tfelt-Hansen J, Winkel BG, van der Werf C, Wijeyeratne YD, Mellor G, Till J, Cohen MC, Tome-Esteban M, Sharma S, Wilde AAM, Cook SA, Bezzina CR, Sheppard MN, Behr ER. Utility of postmortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol. 2017; 69: 2134-2145. doi: 10.1016/j.jacc.2017.02.046.
16. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17: 405-424. doi: 10.1038/gim.2015.30.
17. Ruark E, Münz M, Renwick A, Clarke M, Ramsay E, Hanks S, Mahamdallie S, Elliott A, Seal S, Strydom A, Gerton L, Rahman N. The ICR1000 UK exome series: a resource of gene variation in an outbred population. F1000Res. 2015; 4: 883. doi: 10.12688/f1000research.7049.1.
18. Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, Mc-Carroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG; Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016; 536: 285-291. doi: 10.1038/nature19057.
19. Clarke L, Zheng-Bradley X, Smith R, Kulesha E, Xiao C, Toneva I, Vaughan B, Preuss D, Leinonen R, Shumway M, Sherry S, Flicek P; 1000 Genomes Project Consortium. The 1000 Genomes Project: data management and community access. Nat Methods. 2012; 9: 459-462. doi: 10.1038/nmeth.1974.
20. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995; 80: 805-811.
21. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O'Brien RE, Schulze-Bahr E, Keating MT, Towbin JA, Wang Q. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998; 392: 293-296. doi: 10.1038/32675.
22. Wan X, Chen S, Sadeghpour A, Wang Q, Kirsch GE. Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation. Am J Physiol Heart Circ Physiol. 2001; 280: H354-H360. doi: 10.1152/ajpheart.2001.280.1.H354.
23. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Brignole M, Giordano U, Giovannini T, Menozzi C, Bloise R, Crotti L, Terreni L, Schwartz PJ. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: a prospective evaluation of 52 families. Circulation. 2000; 102: 2509-2515.
24. Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, Jang W, Katz K, Ovetsky M, Riley G, Sethi A, Tully R, Villamarin-Salomon R, Rubinstein W, Maglott DR. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 2016; 44(D1): D862-D868. doi: 10.1093/nar/gkv1222.
25. 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: 619-628. doi: 10.1056/NEJMoa1110186.
26. Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet. 1998; 19: 402-403. doi: 10.1038/1300.
27. He Y, Zhang Z, Hong D, Dai Q, Jiang T. Myocardial fibrosis in desmin-related hypertrophic cardiomyopathy. J Cardiovasc Magn Reson. 2010; 12: 68. doi: 10.1186/1532-429X-12-68.
28. Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999; 100: 461-464.
29. Ackerman JP, Bartos DC, Kapplinger JD, Tester DJ, Delisle BP, Ackerman MJ. The promise and peril of precision medicine: phenotyping still matters most. Mayo Clin Proc. 2016; 91: 1606-1616.
30. Kupershmidt S, Yang IC, Sutherland M, Wells KS, Yang T, Yang P, Balser JR, Roden DM. Cardiac-enriched LIM domain protein fhl2 is required to generate I(Ks) in a heterologous system. Cardiovasc Res. 2002; 56: 93-103.
31. Kapa S, Tester DJ, Salisbury BA, Harris-Kerr C, Pungliya MS, Alders M, Wilde AA, Ackerman MJ. Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009; 120: 1752-1760. doi: 10.1161/CIRCULATIONAHA.109.863076.
32. Refsgaard L, Holst AG, Sadjadieh G, Haunsø S, Nielsen JB, Olesen MS. High prevalence of genetic variants previously associated with LQT syndrome in new exome data. Eur J Hum Genet. 2012; 20: 905-908. doi: 10.1038/ejhg.2012.23.
33. Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet. 2013; 14: 681-691. doi: 10.1038/nrg3555.