Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity

Frontiers in Cardiovascular Medicine

Volumn 3, Issue , 2016, Pages

  Garcia, John ^a   Tahiliani, Jackie ^a   Johnson, Nicole Marie ^a   Aguilar, Sienna ^a   Beltran, Daniel ^a   Daly, Amy ^a   Decker, Emily ^a   Haverfield, Eden ^a   Herrera, Blanca ^a   Murillo, Laura ^a   Nykamp, Keith ^a   Topper, Scott ^a  

^a Invitae Corporation ^*  (United States)

Author keywords

arrhythmias; ARVD C; cardiomyopathies; curation; genetic testing

Indexed keywords

EID: 84995339053     PISSN: None     EISSN: 2297055X     Source Type: Journal    
DOI: 10.3389/fcvm.2016.00020     Document Type: Article

References (44)

1. Burke W. Clinical validity and clinical utility of genetic tests. Curr Protoc Hum Genet (2009) Chapter 9:Unit9.15.10.1002/0471142905.hg0915s6019170033
2. Botkin JR, Teutsch SM, Kaye CI, Hayes M, Haddow JE, Bradley LA, et al. EGAPP Working Group. Outcomes of interest in evidence-based evaluations of genetic tests. Genet Med (2010) 12(4):228–35.10.1097/GIM.0b013e3181cdde04
3. Burke W. Genetic tests: clinical validity and clinical utility. Curr Protoc Hum Genet (2014) 81:9.15.1–8.10.1002/0471142905.hg0915s8124763995
4. Abraham MR, Bottomley PA, Dimaano VL, Pinheiro A, Steinberg A, Traill TA, et al. Creatine kinase adenosine triphosphate and phosphocreatine energy supply in a single kindred of patients with hypertrophic cardiomyopathy. Am J Cardiol (2013) 112(6):861–6.10.1016/j.amjcard.2013.05.01723751935
5. Epstein ND, Cohn GM, Cyran F, Fananapazir L. Differences in clinical expression of hypertrophic cardiomyopathy associated with two distinct mutations in the beta-myosin heavy chain gene. A 908Leu – Val mutation and a 403Arg – Gln mutation. Circulation (1992) 86(2):345–52.10.1161/01.CIR.86.2.345
6. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell (1990) 62(5):999–1006.10.1016/0092-8674(90)90274-I1975517
7. Woo A, Rakowski H, Liew JC, Zhao MS, Liew CC, Parker TG, et al. Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Heart (2003) 89(10):1179–85.10.1136/heart.89.10.117912975413
8. Belus A, Piroddi N, Scellini B, Tesi C, D’Amati G, Girolami F, et al. The familial hypertrophic cardiomyopathy-associated myosin mutation R403Q accelerates tension generation and relaxation of human cardiac myofibrils. J Physiol (2008) 586(15):3639–44.10.1113/jphysiol.2008.15595218565996
9. Cuda G, Fananapazir L, Epstein ND, Sellers JR. The in vitro motility activity of beta-cardiac myosin depends on the nature of the beta-myosin heavy chain gene mutation in hypertrophic cardiomyopathy. J Muscle Res Cell Motil (1997) 18(3):275–83.10.1023/A:10186139075749172070
10. Roopnarine O, Leinwand LA. Functional analysis of myosin mutations that cause familial hypertrophic cardiomyopathy. Biophys J (1998) 75(6):3023–30.10.1016/S0006-3495(98)77743-49826622
11. Volkmann N, Lui H, Hazelwood L, Trybus KM, Lowey S, Hanein D. The R403Q myosin mutation implicated in familial hypertrophic cardiomyopathy causes disorder at the actomyosin interface. PLoS One (2007) 2(11):e1123.10.1371/journal.pone.000112317987111
12. Palmiter KA, Tyska MJ, Haeberle JR, Alpert NR, Fananapazir L, Warshaw DM. R403Q and L908V mutant beta-cardiac myosin from patients with familial hypertrophic cardiomyopathy exhibit enhanced mechanical performance at the single molecule level. J Muscle Res Cell Motil (2000) 21(7):609–20.10.1023/a:1005678905119
13. Yamashita H, Tyska MJ, Warshaw DM, Lowey S, Trybus KM. Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy. J Biol Chem (2000) 275(36):28045–52.10.1074/jbc.M00548520010882745
14. Geisterfer-Lowrance AA, Christe M, Conner DA, Ingwall JS, Schoen FJ, Seidman CE, et al. A mouse model of familial hypertrophic cardiomyopathy. Science (1996) 272(5262):731–4.10.1126/science.272.5262.7318614836
15. Marian AJ, Wu Y, Lim DS, McCluggage M, Youker K, Yu QT, et al. A transgenic rabbit model for human hypertrophic cardiomyopathy. J Clin Invest (1999) 104(12):1683–92.10.1172/JCI795610606622
16. Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, et al. The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat (2009) 30(11):1486–511.10.1002/humu.2110619862833
17. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M. Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet (1999) 89(3):137–46.10.1002/(SICI)1096-8628(19990924)89:3<137::AID-AJMG4>3.0.CO;2-C10704188
18. Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A. Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. Europace (2012) 14(12):1799–806.10.1093/europace/eus11122539601
19. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation (1993) 88(2):782–4.10.1161/01.CIR.88.2.782
20. Giudicessi JR, Ackerman MJ. Genotype- and phenotype-guided management of congenital long QT syndrome. Curr Probl Cardiol (2013) 38(10):417–55.10.1016/j.cpcardiol.2013.08.00124093767
21. Mazzanti A, Kanthan A, Monteforte N, Memmi M, Bloise R, Novelli V, et al. Novel insight into the natural history of short QT syndrome. J Am Coll Cardiol (2014) 63:1300–8.10.1016/j.jacc.2013.09.07824291113
22. Giustetto C, Schimpf R, Mazzanti A, Scrocco C, Maury P, Anttonen O, et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol (2011) 58:587–95.10.1016/j.jacc.2011.03.03821798421
23. Bellocq C, van Ginneken AC, Bezzina CR, Alders M, Escande D, Mannens MM, et al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation (2004) 109(20):2394–7.10.1161/01.CIR.0000130409.72142.FE15159330
24. Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E, et al. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc Res (2005) 68(3):433–40.10.1016/j.cardiores.2005.06.02316109388
25. Behr ER, Savio-Galimberti E, Barc J, Holst AG, Petropoulou E, Prins BP, et al. Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study. Cardiovasc Res (2015) 106(3):520–9.10.1093/cvr/cvv04225691538
26. Hu D, Barajas-Martínez H, Pfeiffer R, Dezi F, Pfeiffer J, Buch T, et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol (2014) 64(1):66–79.10.1016/j.jacc.2014.04.03224998131
27. Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation (1993) 87:1854–65.10.1161/01.CIR.87.6.1854
28. Milasin J, Muntoni F, Severini GM, Bartoloni L, Vatta M, Krajinovic M, et al. A point mutation in the 5’ splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. Hum Mol Genet (1996) 5:73–9.10.1093/hmg/5.1.738789442
29. Bies RD, Maeda M, Roberds SL, Holder E, Bohlmeyer T, Young JB, et al. A 5’ dystrophin duplication mutation causes membrane deficiency of alpha-dystroglycan in a family with X-linked cardiomyopathy. J Mol Cell Cardiol (1997) 29:3175–88.10.1006/jmcc.1997.05689441825
30. Kimura S, Ikezawa M, Ozasa S, Ito K, Ueno H, Yoshioka K, et al. Novel mutation in splicing donor of dystrophin gene first exon in a patient with dilated cardiomyopathy but no clinical signs of skeletal myopathy. J Child Neurol (2007) 22:901–6.10.1177/088307380730470517715288
31. Diegoli M, Grasso M, Favalli V, Serio A, Gambarin FI, Klersy C, et al. Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects. J Am Coll Cardiol (2011) 58(9):925–34.10.1016/j.jacc.2011.01.07221851881
32. Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, et al. Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet (2009) 85(3):338–53.10.1016/j.ajhg.2009.07.01519716112
33. Friedrich FW, Wilding BR, Reischmann S, Crocini C, Lang P, Charron P, et al. Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. Hum Mol Genet (2012) 21(14):3237–54.10.1093/hmg/dds15722523091
34. Hartmannova H, Kubanek M, Sramko M, Piherova L, Noskova L, Hodanova K, et al. Isolated X-linked hypertrophic cardiomyopathy caused by a novel mutation of the four-and-a-half LIM domain 1 gene. Circ Cardiovasc Genet (2013) 6(6):543–51.10.1161/CIRCGENETICS.113.00024524114807
35. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, et al. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med (2015) 17(11):880–8.10.1038/gim.2014.20525611685
36. Biagini E, Coccolo F, Ferlito M, Perugini E, Rocchi G, Bacchi-Reggiani L, et al. Dilated-hypokinetic evolution of hypertrophic cardiomyopathy: prevalence, incidence, risk factors, and prognostic implications in pediatric and adult patients. J Am Coll Cardiol (2005) 46(8):1543–50.10.1016/j.jacc.2005.04.06216226182
37. Forleo C, Carmosino M, Resta N, Rampazzo A, Valecce R, Sorrentino S, et al. Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy. PLoS One (2015) 10(4):e0121723.10.1371/journal.pone.012172325837155
38. Hoogendijk MG. Diagnostic dilemmas: overlapping features of Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy. Front Physiol (2012) 3:144.10.3389/fphys.2012.0014422654761
39. 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 Transl Sci (2010) 3(3):90–7.10.1111/j.1752-8062.2010.00198.x20590677
40. McGregor SM, Husain AN. A brief review and update of the clinicopathologic diagnosis of arrhythmogenic cardiomyopathy. Arch Pathol Lab Med (2015) 139(9):1181–6.10.5858/arpa.2014-0114-RS26317457
41. McNair WP, Ku L, Taylor MR, Fain PR, Dao D, Wolfel E, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation (2004) 110(15):2163–7.10.1161/01.CIR.0000144458.58660.BB15466643
42. 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). Heart Rhythm (2011) 8(8):1308–39.10.1016/j.hrthm.2011.05.020
43. ClinGen. Clinical Validity Classifications as of October 2015. (2015). Available from: https://www.clinicalgenome.org/site/assets/files/2657/current_clinical_validity_classifications.pdf
44. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Lora A, Bean LJH, et al., editors. GeneReviews. Seattle: University of Washington (1993-2016). Available from: http://www.ncbi.nlm.nih.gov/books/NBK1116/