A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot

European Journal of Human Genetics

Volumn 21, Issue 1, 2013, Pages 69-75

  Guida, Valentina ^a   Ferese, Rosangela ^a,b   Rocchetti, Marcella ^c   Bonetti, Monica ^d   Sarkozy, Anna ^a,j   Cecchetti, Serena ^e   Gelmetti, Vania ^a   Lepri, Francesca ^f   Copetti, Massimiliano ^a   Lamorte, Giuseppe ^a   Cristina Digilio, Maria ^f   Marino, Bruno ^g,h   Zaza, Antonio ^c   Den Hertog, Jeroen ^d,i   Dallapiccola, Bruno ^f   De Luca, Alessandro ^a  

^a CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c UNIVERSITY OF MILANO BICOCCA   (Italy)

^d UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^e ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^f BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

^g SAPIENZA UNIVERSITY OF ROME   (Italy)

^h Eleonora Lorillard Spencer Cenci Foundation   (Italy)

ⁱ LEIDEN UNIVERSITY   (Netherlands)

^j NEWCASTLE UNIVERSITY   (United Kingdom)

more..

Author keywords

1q21.1; congenital heart disease; connexin 40; GJA5; tetralogy of Fallot

Indexed keywords

CONNEXIN 40; DYE;

ANIMAL EXPERIMENT; ARTICLE; CARBOXY TERMINAL SEQUENCE; CARDIOVASCULAR RISK; CELL CONTACT; CHROMOSOME; CONFOCAL MICROSCOPY; CONTROLLED STUDY; EXON; FALLOT TETRALOGY; GAP JUNCTION; GENE MUTATION; GENETIC ANALYSIS; GENETIC SCREENING; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HETEROZYGOTE; HUMAN; IMMUNOFLUORESCENCE TEST; MAJOR CLINICAL STUDY; MISSENSE MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PULMONARY VALVE ATRESIA;

AMINO ACID SUBSTITUTION; ANIMALS; CHROMOSOMES, HUMAN, PAIR 1; CONNEXINS; EMBRYO, NONMAMMALIAN; FLUORESCENT DYES; GAP JUNCTIONS; GENETIC PREDISPOSITION TO DISEASE; HEART; HETEROZYGOTE; HUMANS; MICROINJECTIONS; MUTATION; MUTATION, MISSENSE; MYOCARDIUM; PULMONARY ATRESIA; TETRALOGY OF FALLOT; ZEBRAFISH;

DANIO RERIO; MUS;

EID: 84871255563     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2012.109     Document Type: Article

References (49)

1. Ferencz C, Rubin JD, McCarter RJ et al: Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol 1985; 121: 31-36.
2. Amati F, Mari A, Digilio MC et al: 22q11 deletions in isolated and syndromic patients with tetralogy of Fallot. Hum Genet 1995; 95: 479-482.
3. Goldmuntz E, Clark BJ, Mitchell LE et al: Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 1998; 32: 492-498.
4. Goldmuntz E, Geiger E, Benson DW: NKX2.5 mutations in patients with tetralogy of fallot. Circulation 2001; 104: 2565-2568.
5. McElhinney DB, Geiger E, Blinder J, Benson DW, Goldmuntz E: NKX2.5 mutations in patients with congenital heart disease. J Am Coll Cardiol 2003; 42: 1650-1655.
6. Nemer G, Fadlalah F, Usta J et al: A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot. Hum Mutat 2006; 27: 293-294.
7. Tomita-Mitchell A, Maslen CL, Morris CD, Garg V, Goldmuntz E: GATA4 sequence variants in patients with congenital heart disease. J Med Genet 2007; 44: 779-783.
8. De Luca A, Sarkozy A, Ferese R et al: New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle. Clin Genet 2011; 80: 184-190.
9. Roessler E, Ouspenskaia MV, Karkera JD et al: Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly. Am J Hum Genet 2008; 83: 18-29.
10. Garg V, Muth AN, Ransom JF et al: Mutations in NOTCH1 cause aortic valve disease. Nature 2005; 437: 270-274.
11. Eldadah ZA, Hamosh A, Biery NJ et al: Familial Tetralogy of Fallot caused by mutation in the jagged1 gene. Hum Mol Genet 2001; 10: 163-169.
12. Guida V, Chiappe F, Ferese R et al: Novel and recurrent JAG1 mutations in patients with tetralogy of Fallot. Clin Genet 2011; 80: 591-594.
13. Karkera JD, Lee JS, Roessler E et al: Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans. Am J Hum Genet 2007; 81: 987-994.
14. Roessler E, Pei W, Ouspenskaia MV et al: Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly. Mol Genet Metab 2009; 98: 225-234.
15. Schott JJ, Benson DW, Basson CT et al: Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281: 108-111.
16. Garg V, Kathiriya IS, Barnes R et al: GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 2003; 424: 443-447.
17. De Luca A, Sarkozy A, Consoli F et al: Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart 2010; 96: 673-677.
18. Greenway SC, Pereira AC, Lin JC et al: De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat Genet 2009; 41: 931-935.
19. Soemedi R, Topf A, Wilson IJ et al: Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls. Hum Mol Genet 2012; 21: 1513-1520.
20. Gu H, Smith FC, Taffet SM, Delmar M: High incidence of cardiac malformations in connexin40-deficient mice. Circ Res 2003; 93: 201-206.
21. Gollob MH, Jones DL, Krahn AD et al: Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med 2006; 354: 2677-2688.
22. Yang YQ, Liu X, Zhang XL et al: Novel connexin40 missense mutations in patients with familial atrial fibrillation. Europace 2010; 12: 1421-1427.
23. Yang YQ, Zhang XL, Wang XH et al: Connexin40 nonsense mutation in familial atrial fibrillation. Int J Mol Med 2010; 26: 605-610.
24. Westerfield M: The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). University of Oregon Press: Eugene, OR, 1995.
25. Thisse C, Thisse B, Schilling TF, Postlethwait JH: Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail and no tail mutant embryos. Development 1993; 119: 1203-1215.
26. Yelon D, Horne SA, Stainier DY: Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish. Dev Biol 1999; 214: 23-37.
27. Gros D, Dupays L, Alcolea S, Meysen S, Miquerol L, Theveniau-Ruissy M: Genetically modified mice: tools to decode the functions of connexins in the heart-new models for cardiovascular research. Cardiovasc Res 2004; 62: 299-308.
28. Pfenniger A, Wohlwend A, Kwak BR: Mutations in connexin genes and disease. Eur J Clin Invest 2011; 41: 103-116.
29. Sarkozy A, Conti E, Neri C et al: Spectrum of atrial septal defects associated with mutations of NKX2.5 and GATA4 transcription factors. J Med Genet 2005; 42: e16.
30. Rauch R, Hofbeck M, Zweier C et al: Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot. J Med Genet 2010; 47: 321-331.
31. Brunetti-Pierri N, Berg JS, Scaglia F et al: Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat Genet 2008; 40: 1466-1471.
32. Mefford HC, Eichler EE: Duplication hotspots, rare genomic disorders, and common disease. Curr Opin Genet Dev 2009; 19: 196-204.
33. Mefford HC, Sharp AJ, Baker C et al: Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 2008; 359: 1685-1699.
34. Christiansen J, Dyck JD, Elyas BG et al: Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease. Circ Res 2004; 94: 1429-1435.
35. Erdogan F, Larsen LA, Zhang L et al: High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease. J Med Genet 2008; 45: 704-709.
36. Digilio MC, Marino B, Grazioli S, Agostino D, Giannotti A, Dallapiccola B: Comparison of occurrence of genetic syndromes in ventricular septal defect with pulmonic stenosis (classic tetralogy of Fallot) versus ventricular septal defect with pulmonic atresia. Am J Cardiol 1996; 77: 1375-1376.
37. Marino B, Digilio MC, Toscano A et al: Anatomic patterns of conotruncal defects associated with deletion 22q11. Genet Med 2001; 3: 45-48.
38. van Veen AA, van Rijen HV, Opthof T: Cardiac gap junction channels: modulation of expression and channel properties. Cardiovasc Res 2001; 51: 217-229.
39. Kirchhoff S, Kim JS, Hagendorff A et al: Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double-deficient mice. Circ Res 2000; 87: 399-405.
40. Bouvier D, Kieken F, Kellezi A, Sorgen PL: Structural changes in the carboxyl terminus of the gap junction protein connexin 40 caused by the interaction with c-Src and zonula occludens-1. Cell Commun Adhes 2008; 15: 107-118.
41. Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradovic Z: Intrinsic disorder and protein function. Biochemistry 2002; 41: 6573-6582.
42. Dunker AK, Obradovic Z: The protein trinity-linking function and disorder. Nat Biotechnol 2001; 19: 805-806.
43. Zhou L, Kasperek EM, Nicholson BJ: Dissection of the molecular basis of pp60 (v-src) induced gating of connexin 43 gap junction channels. J Cell Biol 1999; 144: 1033-1045.
44. Lin R, Warn-Cramer BJ, Kurata WE, Lau AF: v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication. J Cell Biol 2001; 154: 815-827.
45. Jia CY, Nie J, Wu C, Li C, Li SS: Novel Src homology 3 domain-binding motifs identified from proteomic screen of a Pro-rich region. Mol Cell Proteomics 2005; 4: 1155-1166.
46. Duffy HS, Ashton AW, O'Donnell P et al: Regulation of connexin43 protein complexes by intracellular acidification. Circ Res 2004; 94: 215-222.
47. Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M: Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem 1998; 273: 12725-12731.
48. Hunter AW, Barker RJ, Zhu C, Gourdie RG: Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell 2005; 16: 5686-5698.
49. Barker RJ, Price RL, Gourdie RG: Increased association of ZO-1 with connexin43 during remodeling of cardiac gap junctions. Circ Res 2002; 90: 317-324.