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Article

A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias

  • Authors:
    • Fang Yuan
    • Xing-Biao Qiu
    • Ruo-Gu Li
    • Xin-Kai Qu
    • Juan Wang
    • Ying-Jia Xu
    • Xu Liu
    • Wei-Yi Fang
    • Yi-Qing Yang
    • De-Ning Liao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China
  • Pages: 478-486
    |
    Published online on: December 9, 2014
       https://doi.org/10.3892/ijmm.2014.2029
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Abstract

Dilated cardiomyopathy (DCM) is the most prevalent type of primary myocardial disease, which is the third most common cause of heart failure and the most frequent reason for heart transplantation. Aggregating evidence demonstrates that genetic risk factors are involved in the pathogenesis of idiopathic DCM. Nevertheless, DCM is of remarkable genetic heterogeneity and the genetic defects underpinning DCM in an overwhelming majority of patients remain unknown. In the present study, the whole coding exons and splice junction sites of the NKX2-5 gene, which encodes a homeodomain transcription factor crucial for cardiac development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient harboring an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for the NKX2-5 gene. The functional effect of the mutant NKX2-5 was characterized in contrast to its wild-type counterpart using a dual-luciferase reporter assay system. As a result, a novel heterozygous NKX2-5 mutation, p.S146W, was identified in a family with DCM inherited as an autosomal dominant trait, which co-segregated with DCM in the family with complete penetrance. Notably, the mutation carriers also had arrhythmias, such as paroxysmal atrial fibrillation and atrioventricular block. The missense mutation was absent in 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily among species. Functional analysis revealed that the NKX2-5 mutant was associated with a significantly reduced transcriptional activity. The findings expand the mutational spectrum of NKX2-5 linked to DCM and provide novel insight into the molecular mechanisms underlying DCM, contributing to the antenatal prophylaxis and allele-specific management of DCM.
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1 

Garcia-Pavia P, Cobo-Marcos M, Guzzo-Merello G, Gomez-Bueno M, Bornstein B, Lara-Pezzi E, Segovia J and Alonso-Pulpon L: Genetics in dilated cardiomyopathy. Biomark Med. 7:517–533. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Hershberger RE, Hedges DJ and Morales A: Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 10:531–547. 2013. View Article : Google Scholar : PubMed/NCBI

3 

McNally EM, Golbus JR and Puckelwartz MJ: Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest. 123:19–26. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Koutalas E, Kanoupakis E and Vardas P: Sudden cardiac death in non-ischemic dilated cardiomyopathy: a critical appraisal of existing and potential risk stratification tools. Int J Cardiol. 167:335–341. 2013. View Article : Google Scholar

5 

Yoshikawa T: Contribution of acquired factors to the pathogenesis of dilated cardiomyopathy. The cause of dilated cardiomyopathy: genetic or acquired? (Acquired-Side). Circ J. 75:1766–1773. 2011. View Article : Google Scholar

6 

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 and Ellinor PT: Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 9:390–396. 2012. View Article : Google Scholar :

7 

Wahbi K, Béhin A, Bécane HM, Leturcq F, Cossée M, Laforêt P, Stojkovic T, Carlier P, Toussaint M, Gaxotte V, Cluzel P, Eymard B and Duboc D: Dilated cardiomyopathy in patients with mutations in anoctamin 5. Int J Cardiol. 168:76–79. 2013. View Article : Google Scholar

8 

Flack E and Kannankeril PJ: The genetics of dilated cardiomyopathy. Heart Rhythm. 9:397–398. 2012. View Article : Google Scholar

9 

Pikkarainen S, Tokola H, Kerkelä R and Ruskoaho H: GATA transcription factors in the developing and adult heart. Cardiovasc Res. 63:196–207. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Oka T, Xu J and Molkentin JD: Re-employment of developmental transcription factors in adult heart disease. Semin Cell Dev Biol. 18:117–131. 2007. View Article : Google Scholar

11 

Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DY and Poss KD: Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes. Nature. 464:601–605. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Akazawa H and Komuro I: Cardiac transcription factor Csx/Nkx2–5: its role in cardiac development and diseases. Pharmacol Ther. 107:252–268. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Kasahara A, Cipolat S, Chen Y, Dorn GW II and Scorrano L: Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling. Science. 342:734–737. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Cai H, Katoh-Kurasawa M, Muramoto T, Santhanam B, Long Y, Li L, Ueda M, Iglesias PA, Shaulsky G and Devreotes PN: Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer. Science. 343:12495312014. View Article : Google Scholar : PubMed/NCBI

15 

Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC and Srivastava D: GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature. 424:443–447. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Rajagopal SK, Ma Q, Obler D, Shen J, Manichaikul A, Tomita-Mitchell A, Boardman K, Briggs C, Garg V, Srivastava D, Goldmuntz E, Broman KW, Benson DW, Smoot LB and Pu WT: Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol. 43:677–685. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Yang YQ, Li L, Wang J, Liu XY, Chen XZ, Zhang W, Wang XZ, Jiang JQ, Liu X and Fang WY: A novel GATA4 loss-of-function mutation associated with congenital ventricular septal defect. Pediatr Cardiol. 33:539–546. 2012. View Article : Google Scholar

18 

Wang J, Sun YM and Yang YQ: Mutation spectrum of the GATA4 gene in patients with idiopathic atrial fibrillation. Mol Biol Rep. 39:8127–8135. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Yang YQ, Wang J, Liu XY, Chen XZ, Zhang W and Wang XZ: Mutation spectrum of GATA4 associated with congenital atrial septal defects. Arch Med Sci. 9:976–983. 2013. View Article : Google Scholar

20 

Yang YQ, Gharibeh L, Li RG, Xin YF, Wang J, Liu ZM, Qiu XB, Xu YJ, Xu L, Qu XK, Liu X, Fang WY, Huang RT, Xue S and Nemer G: GATA4 loss-of-function mutations underlie familial tetralogy of fallot. Hum Mutat. 34:1662–1671. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Yang YQ, Wang J, Wang XH, Wang Q, Tan HW, Zhang M, Shen FF, Jiang JQ, Fang WY and Liu X: Mutational spectrum of the GATA5 gene associated with familial atrial fibrillation. Int J Cardiol. 157:305–307. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Gu JY, Xu JH, Yu H and Yang YQ: Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation. Clinics (Sao Paulo). 67:1393–1399. 2012. View Article : Google Scholar

23 

Jiang JQ, Li RG, Wang J, Liu XY, Xu YJ, Fang WY, Chen XZ, Zhang W, Wang XZ and Yang YQ: Prevalence and spectrum of GATA5 mutations associated with congenital heart disease. Int J Cardiol. 165:570–573. 2013. View Article : Google Scholar

24 

Wei D, Bao H, Zhou N, Zheng GF, Liu XY and Yang YQ: GATA5 loss-of-function mutation responsible for the congenital ventriculoseptal defect. Pediatr Cardiol. 34:504–511. 2013. View Article : Google Scholar

25 

Wei D, Bao H, Liu XY, Zhou N, Wang Q, Li RG, Xu YJ and Yang YQ: GATA5 loss-of-function mutations underlie tetralogy of fallot. Int J Med Sci. 10:34–42. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Wang XH, Huang CX, Wang Q, Li RG, Xu YJ, Liu X, Fang WY and Yang YQ: A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. Int J Mol Med. 31:43–50. 2013.

27 

Shi LM, Tao JW, Qiu XB, Wang J, Yuan F, Xu L, Liu H, Li RG, Xu YJ, Wang Q, Zheng HZ, Li X, Wang XZ, Zhang M, Qu XK and Yang YQ: GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. Int J Mol Med. 33:1219–1226. 2014.PubMed/NCBI

28 

Huang RT, Xue S, Xu YJ, Zhou M and Yang YQ: Somatic GATA5 mutations in sporadic tetralogy of Fallot. Int J Mol Med. 33:1227–1235. 2014.PubMed/NCBI

29 

Zheng GF, Wei D, Zhao H, Zhou N, Yang YQ and Liu XY: A novel GATA6 mutation associated with congenital ventricular septal defect. Int J Mol Med. 29:1065–1071. 2012.PubMed/NCBI

30 

Wang J, Luo XJ, Xin YF, Liu Y, Liu ZM, Wang Q, Li RG, Fang WY, Wang XZ and Yang YQ: Novel GATA6 mutations associated with congenital ventricular septal defect or tetralogy of fallot. DNA Cell Biol. 31:1610–1617. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Yang YQ, Wang XH, Tan HW, Jiang WF, Fang WY and Liu X: Prevalence and spectrum of GATA6 mutations associated with familial atrial fibrillation. Int J Cardiol. 155:494–496. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Yang YQ, Li L, Wang J, Zhang XL, Li RG, Xu YJ, Tan HW, Wang XH, Jiang JQ, Fang WY and Liu X: GATA6 loss-of-function mutation in atrial fibrillation. Eur J Med Genet. 55:520–526. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Li J, Liu WD, Yang ZL and Yang YQ: Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med. 30:783–790. 2012.PubMed/NCBI

34 

Huang RT, Xue S, Xu YJ and Yang YQ: Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot. Int J Mol Med. 31:51–58. 2013.

35 

Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE and Seidman JG: Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science. 281:108–111. 1998. View Article : Google Scholar : PubMed/NCBI

36 

Guntheroth W, Chun L, Patton KK, Matsushita MM, Page RL and Raskind WH: Wenckebach periodicity at rest that normalizes with tachycardia in a family with a NKX2.5 mutation. Am J Cardiol. 110:1646–1650. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Xie WH, Chang C, Xu YJ, Li RG, Qu XK, Fang WY, Liu X and Yang YQ: Prevalence and spectrum of Nkx2.5 mutations associated with idiopathic atrial fibrillation. Clinics (Sao Paulo). 68:777–784. 2013. View Article : Google Scholar

38 

Huang RT, Xue S, Xu YJ, Zhou M and Yang YQ: A novel NKX2.5 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med. 31:1119–1126. 2013.PubMed/NCBI

39 

McCulley DJ and Black BL: Transcription factor pathways and congenital heart disease. Curr Top Dev Biol. 100:253–277. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Li RG, Li L, Qiu XB, Yuan F, Xu L, Li X, Xu YJ, Jiang WF, Jiang JQ, Liu X, Fang WY, Zhang M, Peng LY, Qu XK and Yang YQ: GATA4 loss-of-function mutation underlies familial dilated cardiomyopathy. Biochem Biophys Res Commun. 439:591–596. 2013. View Article : Google Scholar : PubMed/NCBI

41 

Zhao L, Xu JH, Xu WJ, Yu H, Wang Q, Zheng HZ, Jiang WF, Jiang JF and Yang YQ: A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. Int J Mol Med. 33:654–660. 2014.

42 

Brody MJ, Cho E, Mysliwiec MR, Kim TG, Carlson CD, Lee KH and Lee Y: Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4. J Mol Cell Cardiol. 62:237–246. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Lints TJ, Parsons LM, Hartley L, Lyons I and Harvey RP: Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development. 119:419–431. 1993.PubMed/NCBI

44 

Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L and Harvey RP: Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev. 9:1654–1666. 1995. View Article : Google Scholar : PubMed/NCBI

45 

Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME and Harvey RP: An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell. 128:947–959. 2007. View Article : Google Scholar : PubMed/NCBI

46 

Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SY, Benson DW, Silberbach M, Shou W and Chien KR: Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomy-opathy and complete heart block. Cell. 117:373–386. 2004. View Article : Google Scholar : PubMed/NCBI

47 

Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Marks MH, Walker AJ, Seki T, Oh SP, Lu JT, Sumners C, Raizada MK, Horikoshi N, Weinberg EO, Yasui K, Ikeda Y, Chien KR and Kasahara H: Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res. 103:580–590. 2008. View Article : Google Scholar : PubMed/NCBI

48 

Takeda M, Briggs LE, Wakimoto H, Marks MH, Warren SA, Lu JT, Weinberg EO, Robertson KD, Chien KR and Kasahara H: Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest. 89:983–993. 2009. View Article : Google Scholar : PubMed/NCBI

49 

Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S, Smalls O, Johnson MC, Watson MS, Seidman JG, Seidman CE, Plowden J and Kugler JD: Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest. 104:1567–1573. 1999. View Article : Google Scholar : PubMed/NCBI

50 

Kirk EP, Sunde M, Costa MW, Rankin SA, Wolstein O, Castro ML, Butler TL, Hyun C, Guo G, Otway R, Mackay JP, Waddell LB, Cole AD, Hayward C, Keogh A, Macdonald P, Griffiths L, Fatkin D, Sholler GF, Zorn AM, Feneley MP, Winlaw DS and Harvey RP: Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Am J Hum Genet. 81:280–291. 2007. View Article : Google Scholar : PubMed/NCBI

51 

Brody MJ, Hacker TA, Patel JR, Feng L, Sadoshima J, Tevosian SG, Balijepalli RC, Moss RL and Lee Y: Ablation of the cardiac-specific gene leucine-rich repeat containing 10 (Lrrc10) results in dilated cardiomyopathy. PLoS One. 7:e516212012. View Article : Google Scholar : PubMed/NCBI

52 

Elliott P, O’Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard MN, Carr-White G, Pantazis A and McKenna WJ: Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy. Circ Cardiovasc Genet. 3:314–322. 2010. View Article : Google Scholar : PubMed/NCBI

53 

Costa MW, Guo G, Wolstein O, Vale M, Castro ML, Wang L, Otway R, Riek P, Cochrane N, Furtado M, Semsarian C, Weintraub RG, Yeoh T, Hayward C, Keogh A, Macdonald P, Feneley M, Graham RM, Seidman JG, Seidman CE, Rosenthal N, Fatkin D and Harvey RP: Functional characterization of a novel mutation in NKX2-5 associated with congenital heart disease and adult-onset cardiomyopathy. Circ Cardiovasc Genet. 6:238–247. 2013. View Article : Google Scholar : PubMed/NCBI

54 

Kasahara H, Lee B, Schott JJ, Benson DW, Seidman JG, Seidman CE and Izumo S: Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease. J Clin Invest. 106:299–308. 2000. View Article : Google Scholar : PubMed/NCBI

55 

Goldmuntz E, Geiger E and Benson DW: NKX2.5 mutations in patients with tetralogy of fallot. Circulation. 104:2565–2568. 2001. View Article : Google Scholar : PubMed/NCBI

56 

Stallmeyer B, Fenge H, Nowak-Göttl U and Schulze-Bahr E: Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease. Clin Genet. 78:533–540. 2010. View Article : Google Scholar : PubMed/NCBI

57 

Beffagna G, Cecchetto A, Dal Bianco L, Lorenzon A, Angelini A, Padalino M, Vida V, Bhattacharya S, Stellin G, Rampazzo A and Daliento L: R25C mutation in the NKX2.5 gene in Italian patients affected with non-syndromic and syndromic congenital heart disease. J Cardiovasc Med (Hagerstown). 14:582–586. 2013. View Article : Google Scholar

58 

Dentice M, Cordeddu V, Rosica A, Ferrara AM, Santarpia L, Salvatore D, Chiovato L, Perri A, Moschini L, Fazzini C, Olivieri A, Costa P, Stoppioni V, Baserga M, De Felice M, Sorcini M, Fenzi G, Di Lauro R, Tartaglia M and Macchia PE: Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab. 91:1428–1433. 2006. View Article : Google Scholar : PubMed/NCBI

59 

Komuro I and Izumo S: Csx: a murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA. 90:814581491993. View Article : Google Scholar

60 

Kasahara H, Bartunkova S, Schinke M, Tanaka M and Izumo S: Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ Res. 82:936–946. 1998. View Article : Google Scholar : PubMed/NCBI

61 

Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L and Harvey RP: Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3’UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol. 46:431–439. 2002.

62 

Schlesinger J, Schueler M, Grunert M, Fischer JJ, Zhang Q, Krueger T, Lange M, Tönjes M, Dunkel I and Sperling SR: The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs. PLoS Genet. 7:e10013132011. View Article : Google Scholar : PubMed/NCBI

63 

Shin CH, Liu ZP, Passier R, Zhang CL, Wang DZ, Harris TM, Yamagishi H, Richardson JA, Childs G and Olson EN: Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell. 110:725–735. 2002. View Article : Google Scholar : PubMed/NCBI

64 

Tanaka M, Chen Z, Bartunkova S, Yamasaki N and Izumo S: The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 126:1269–1280. 1999.PubMed/NCBI

65 

Biben C, Weber R, Kesteven S, Stanley E, McDonald L, Elliott DA, Barnett L, Köentgen F, Robb L, Feneley M and Harvey RP: Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ Res. 87:888–895. 2000. View Article : Google Scholar : PubMed/NCBI

66 

Biben C and Harvey RP: Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development. Genes Dev. 11:1357–1369. 1997. View Article : Google Scholar : PubMed/NCBI

67 

Zou Y, Evans S, Chen J, Kuo HC, Harvey RP and Chien KR: CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2–5 homeobox gene pathway. Development. 124:793–804. 1997.PubMed/NCBI

68 

Thompson JT, Rackley MS and O’Brien TX: Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload. Am J Physiol. 274:H1569–H1573. 1998.PubMed/NCBI

69 

Saadane N, Alpert L and Chalifour LE: Expression of immediate early genes, GATA-4, and Nkx-2.5 in adrenergic-induced cardiac hypertrophy and during regression in adult mice. Br J Pharmacol. 127:1165–1176. 1999. View Article : Google Scholar : PubMed/NCBI

70 

Toko H, Zhu W, Takimoto E, Shiojima I, Hiroi Y, Zou Y, Oka T, Akazawa H, Mizukami M, Sakamoto M, Terasaki F, Kitaura Y, Takano H, Nagai T, Nagai R and Komuro I: Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart. J Biol Chem. 277:24735–24743. 2002. View Article : Google Scholar : PubMed/NCBI

71 

Kasahara H, Wakimoto H, Liu M, Maguire CT, Converso KL, Shioi T, Huang WY, Manning WJ, Paul D, Lawitts J, Berul CI and Izumo S: Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein. J Clin Invest. 108:189–201. 2001. View Article : Google Scholar : PubMed/NCBI

72 

Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R and Komuro I: Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet. 28:276–280. 2001. View Article : Google Scholar : PubMed/NCBI

73 

Sepulveda JL, Belaguli N, Nigam V, Chen CY, Nemer M and Schwartz RJ: GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating early cardiac gene expression. Mol Cell Biol. 18:3405–3415. 1998.PubMed/NCBI

74 

Durocher D, Charron F, Warren R, Schwartz RJ and Nemer M: The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors. EMBO J. 16:5687–5696. 1997. View Article : Google Scholar : PubMed/NCBI

75 

Chen CY and Schwartz RJ: Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription. Mol Cell Biol. 16:6372–6384. 1996.PubMed/NCBI

76 

Song K, Backs J, McAnally J, Qi X, Gerard RD, Richardson JA, Hill JA, Bassel-Duby R and Olson EN: The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases. Cell. 125:453–466. 2006. View Article : Google Scholar : PubMed/NCBI

77 

Kasahara H, Ueyama T, Wakimoto H, Liu MK, Maguire CT, Converso KL, Kang PM, Manning WJ, Lawitts J, Paul DL, Berul CI and Izumo S: Nkx2. 5 homeoprotein regulates expression of gap junction protein connexin 43 and sarcomere organization in postnatal cardiomyocytes. J Mol Cell Cardiol. 35:243–256. 2003. View Article : Google Scholar : PubMed/NCBI

78 

Gutierrez-Roelens I, Sluysmans T, Gewillig M, Devriendt K and Vikkula M: Progressive AV-block and anomalous venous return among cardiac anomalies associated with two novel missense mutations in the CSX/NKX2-5 gene. Hum Mutat. 20:75–76. 2002. View Article : Google Scholar : PubMed/NCBI

79 

Elliott DA, Kirk EP, Yeoh T, Chandar S, McKenzie F, Taylor P, Grossfeld P, Fatkin D, Jones O, Hayes P, Feneley M and Harvey RP: Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations with atrial septal defect and hypoplastic left heart syndrome. J Am Coll Cardiol. 41:2072–2076. 2003. View Article : Google Scholar : PubMed/NCBI

80 

McElhinney DB, Geiger E, Blinder J, Benson DW and Goldmuntz E: NKX2.5 mutations in patients with congenital heart disease. J Am Coll Cardiol. 42:1650–1655. 2003. View Article : Google Scholar : PubMed/NCBI

81 

Reamon-Buettner SM and Borlak J: NKX2-5: an update on this hypermutable homeodomain protein and its role in human congenital heart disease (CHD). Hum Mutat. 31:1185–1194. 2010. View Article : Google Scholar : PubMed/NCBI

82 

Wang J, Xin YF, Liu XY, Liu ZM, Wang XZ and Yang YQ: A novel NKX2-5 mutation in familial ventricular septal defect. Int J Mol Med. 27:369–375. 2011.

83 

Qin X, Xing Q, Ma L, Meng H, Liu Y, Pang S and Yan B: Genetic analysis of an enhancer of the NKX2-5 gene in ventricular septal defects. Gene. 508:106–109. 2012. View Article : Google Scholar : PubMed/NCBI

84 

Huang W, Meng H, Qiao Y, Pang S, Chen D and Yan B: Two novel and functional DNA sequence variants within an upstream enhancer of the human NKX2-5 gene in ventricular septal defects. Gene. 524:152–155. 2013. View Article : Google Scholar : PubMed/NCBI

85 

Yan H, Yuan W, Velculescu VE, Vogelstein B and Kinzler KW: Allelic variation in human gene expression. Science. 297:11432002. View Article : Google Scholar : PubMed/NCBI

86 

Weisfeld-Adams JD, Edelmann L, Gadi IK and Mehta L: Phenotypic heterogeneity in a family with a small atypical microduplication of chromosome 22q11.2 involving TBX1. Eur J Med Genet. 55:732–736. 2012. View Article : Google Scholar : PubMed/NCBI

87 

Smith H, Galmes R, Gogolina E, Straatman-Iwanowska A, Reay K, Banushi B, Bruce CK, Cullinane AR, Romero R, Chang R, Ackermann O, Baumann C, Cangul H, Cakmak Celik F, Aygun C, Coward R, Dionisi-Vici C, Sibbles B, Inward C, Kim CA, Klumperman J, Knisely AS, Watson SP and Gissen P: Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome. Hum Mutat. 33:1656–1664. 2012. View Article : Google Scholar : PubMed/NCBI

88 

Soemedi R, Wilson IJ, Bentham J, Darlay R, Töpf A, Zelenika D, Cosgrove C, Setchfield K, Thornborough C, Granados-Riveron J, Blue GM, Breckpot J, Hellens S, Zwolinkski S, Glen E, Mamasoula C, Rahman TJ, Hall D, Rauch A, Devriendt K, Gewillig M, O’ Sullivan J, Winlaw DS, Bu’Lock F, Brook JD, Bhattacharya S, Lathrop M, Santibanez-Koref M, Cordell HJ, Goodship JA and Keavney BD: Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease. Am J Hum Genet. 91:489–501. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yuan F, Qiu X, Li R, Qu X, Wang J, Xu Y, Liu X, Fang W, Yang Y, Liao D, Liao D, et al: A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. Int J Mol Med 35: 478-486, 2015.
APA
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y. ... Liao, D. (2015). A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. International Journal of Molecular Medicine, 35, 478-486. https://doi.org/10.3892/ijmm.2014.2029
MLA
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y., Liu, X., Fang, W., Yang, Y., Liao, D."A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias". International Journal of Molecular Medicine 35.2 (2015): 478-486.
Chicago
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y., Liu, X., Fang, W., Yang, Y., Liao, D."A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias". International Journal of Molecular Medicine 35, no. 2 (2015): 478-486. https://doi.org/10.3892/ijmm.2014.2029
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan F, Qiu X, Li R, Qu X, Wang J, Xu Y, Liu X, Fang W, Yang Y, Liao D, Liao D, et al: A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. Int J Mol Med 35: 478-486, 2015.
APA
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y. ... Liao, D. (2015). A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. International Journal of Molecular Medicine, 35, 478-486. https://doi.org/10.3892/ijmm.2014.2029
MLA
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y., Liu, X., Fang, W., Yang, Y., Liao, D."A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias". International Journal of Molecular Medicine 35.2 (2015): 478-486.
Chicago
Yuan, F., Qiu, X., Li, R., Qu, X., Wang, J., Xu, Y., Liu, X., Fang, W., Yang, Y., Liao, D."A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias". International Journal of Molecular Medicine 35, no. 2 (2015): 478-486. https://doi.org/10.3892/ijmm.2014.2029
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