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PMID: 23934094 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Of mice and men: molecular genetics of congenital heart disease.

Cellular and molecular life sciences : CMLS ·Vol. 71 ·No. 8 ·2014-04-00 ·Pages 1327-52

Andersen TA, Troelsen Kde L, Larsen LA

Abstract

Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers.

MeSH Terms
Animals Chromosome Aberrations DNA Copy Number Variations/genetics Genes/genetics Genetic Predisposition to Disease/genetics Heart Diseases/congenital,genetics Heterotaxy Syndrome/genetics Humans Mice Models, Biological Molecular Biology/methods Sarcomeres/genetics Signal Transduction/genetics Transcription Factors/genetics
Chemicals
Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Andersen Troels Askhøj
Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
Troelsen Karin de Linde Lind
Larsen Lars Allan
Supplementary Concepts
Laterality Defects, Autosomal Dominant (Disease)
References (288)
288 references, click to expand
  1. Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors.
    Development. 2004 Nov;131(21):5491-502 PMID: 15469978
  2. Coordinating tissue interactions: Notch signaling in cardiac development and disease.
    Dev Cell. 2012 Feb 14;22(2):244-54 PMID: 22340493
  3. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.
    J Clin Invest. 1999 Dec;104(11):1567-73 PMID: 10587520
  4. The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome.
    Cell. 2003 Jun 27;113(7):905-17 PMID: 12837248
  5. Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway.
    Nat Genet. 2004 Nov;36(11):1189-96 PMID: 15475956
  6. WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci.
    EMBO J. 2002 May 1;21(9):2231-41 PMID: 11980720
  7. Germline KRAS mutations cause Noonan syndrome.
    Nat Genet. 2006 Mar;38(3):331-6 PMID: 16474405
  8. Mutations in the human Jagged1 gene are responsible for Alagille syndrome.
    Nat Genet. 1997 Jul;16(3):235-42 PMID: 9207787
  9. Variability in clinical phenotype despite common chromosomal deletion in Smith-Magenis syndrome [del(17)(p11.2p11.2)].
    Genet Med. 2003 Nov-Dec;5(6):430-4 PMID: 14614393
  10. Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.
    Kidney Int. 2011 Dec;80(11):1239-45 PMID: 21866095
  11. Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair.
    Nat Genet. 2009 Sep;41(9):1022-6 PMID: 19684605
  12. Human gene copy number spectra analysis in congenital heart malformations.
    Physiol Genomics. 2012 May 1;44(9):518-41 PMID: 22318994
  13. Congenital heart defects in Kabuki syndrome.
    Am J Med Genet. 2001 May 15;100(4):269-74 PMID: 11343317
  14. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition.
    Cell. 1996 Jul 12;86(1):59-69 PMID: 8689688
  15. CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle.
    Am J Hum Genet. 2002 Mar;70(3):776-80 PMID: 11799476
  16. Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms.
    J Thorac Cardiovasc Surg. 2007 Aug;134(2):290-6 PMID: 17662764
  17. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism.
    J Biol Chem. 2002 Jul 5;277(27):24390-8 PMID: 11994297
  18. The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system.
    J Cell Sci. 1993 Aug;105 ( Pt 4):985-91 PMID: 8227219
  19. GATA4 is a dosage-sensitive regulator of cardiac morphogenesis.
    Dev Biol. 2004 Nov 1;275(1):235-44 PMID: 15464586
  20. Nkx-2.5 gene induction in mice is mediated by a Smad consensus regulatory region.
    Dev Biol. 2002 Apr 15;244(2):243-56 PMID: 11944934
  21. Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities.
    Eur J Hum Genet. 2013 Feb;21(2):173-81 PMID: 22929023
  22. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome.
    Circulation. 2002 Nov 12;106(20):2567-74 PMID: 12427653
  23. Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development.
    Am J Hum Genet. 1999 Mar;64(3):712-21 PMID: 10053005
  24. Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality.
    Nat Genet. 1998 Aug;19(4):333-9 PMID: 9697693
  25. Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
    Dev Dyn. 2010 Jul;239(7):2024-33 PMID: 20549724
  26. Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal.
    J Pediatr. 1999 Dec;135(6):703-6 PMID: 10586172
  27. FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination.
    Nature. 2005 May 12;435(7039):172-7 PMID: 15889083
  28. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).
    J Med Genet. 2008 Feb;45(2):71-80 PMID: 17873117
  29. A unified model for left-right asymmetry? Comparison and synthesis of molecular models of embryonic laterality.
    Dev Biol. 2013 Jul 1;379(1):1-15 PMID: 23583583
  30. A restricted spectrum of NRAS mutations causes Noonan syndrome.
    Nat Genet. 2010 Jan;42(1):27-9 PMID: 19966803
  31. A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.
    Nature. 2009 Jul 9;460(7252):287-91 PMID: 19483677
  32. Smooth-muscle contraction without smooth-muscle myosin.
    Nat Cell Biol. 2000 Jun;2(6):371-5 PMID: 10854329
  33. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.
    PLoS One. 2013;8(4):e60244 PMID: 23560082
  34. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype.
    Am J Hum Genet. 2007 Apr;80(4):633-49 PMID: 17357070
  35. Okihiro syndrome is caused by SALL4 mutations.
    Hum Mol Genet. 2002 Nov 1;11(23):2979-87 PMID: 12393809
  36. Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage.
    Hum Mol Genet. 2004 Aug 1;13(15):1577-85 PMID: 15190012
  37. Congenital heart defects--chromosomal anomalies, syndromes and extracardiac malformations.
    Acta Paediatr. 2007 Aug;96(8):1142-5 PMID: 17590185
  38. High incidence of cardiac malformations in connexin40-deficient mice.
    Circ Res. 2003 Aug 8;93(3):201-6 PMID: 12842919
  39. Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block.
    Curr Biol. 1998 Feb 26;8(5):295-8 PMID: 9501069
  40. The Role of the Geneticist and Genetic Counselor in an ACHD Clinic.
    Prog Pediatr Cardiol. 2012 Aug 1;34(1):15-20 PMID: 23049235
  41. The epidemiology of cardiovascular defects, part 2: a study based on data from three large registries of congenital malformations.
    Pediatr Cardiol. 2003 May-Jun;24(3):222-35 PMID: 12632214
  42. Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.
    Nat Genet. 2006 Mar;38(3):343-9 PMID: 16444274
  43. NOTCH1 mutations in individuals with left ventricular outflow tract malformations reduce ligand-induced signaling.
    Hum Mol Genet. 2008 Sep 15;17(18):2886-93 PMID: 18593716
  44. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice.
    Nature. 2001 Mar 1;410(6824):97-101 PMID: 11242049
  45. Genetic assembly of the heart: implications for congenital heart disease.
    Annu Rev Physiol. 2001;63:451-69 PMID: 11181963
  46. Cardiac-specific activity of an Nkx2-5 enhancer requires an evolutionarily conserved Smad binding site.
    Dev Biol. 2002 Apr 15;244(2):257-66 PMID: 11944935
  47. Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes.
    J Med Genet. 2004 Jun;41(6):433-9 PMID: 15173228
  48. T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers.
    Dev Dyn. 2004 Apr;229(4):763-70 PMID: 15042700
  49. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.
    Science. 2006 Mar 3;311(5765):1287-90 PMID: 16439621
  50. Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome.
    Dev Cell. 2006 Jan;10(1):81-92 PMID: 16399080
  51. New findings concerning cardiovascular manifestations emerging from long-term follow-up of 150 patients with the Williams-Beuren-Beuren syndrome.
    Cardiol Young. 2009 Dec;19(6):563-7 PMID: 19941695
  52. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.
    Nat Genet. 1993 Sep;5(1):11-6 PMID: 7693128
  53. GATA4 sequence variants in patients with congenital heart disease.
    J Med Genet. 2007 Dec;44(12):779-83 PMID: 18055909
  54. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.
    Genes Dev. 1995 Jul 1;9(13):1654-66 PMID: 7628699
  55. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
    Nat Genet. 2007 Aug;39(8):1007-12 PMID: 17603483
  56. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.
    Nat Genet. 2007 Jan;39(1):75-9 PMID: 17143282
  57. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1.
    Nat Genet. 1997 Jul;16(3):243-51 PMID: 9207788
  58. Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.
    Genes Dev. 2002 May 15;16(10):1234-46 PMID: 12023302
  59. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.
    Nat Genet. 1997 Jan;15(1):21-9 PMID: 8988164
  60. Congenital heart disease caused by mutations in the transcription factor NKX2-5.
    Science. 1998 Jul 3;281(5373):108-11 PMID: 9651244
  61. NKX2.5 mutations in patients with tetralogy of fallot.
    Circulation. 2001 Nov 20;104(21):2565-8 PMID: 11714651
  62. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects.
    Am J Hum Genet. 2004 Jan;74(1):93-105 PMID: 14681828
  63. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.
    Nat Genet. 2006 Mar;38(3):294-6 PMID: 16474404
  64. A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning.
    PLoS One. 2011;6(7):e22908 PMID: 21829553
  65. Congenital heart disease in CHARGE association.
    Pediatr Cardiol. 1993 Mar;14(2):75-81 PMID: 8469635
  66. Rare copy number variations in adults with tetralogy of Fallot implicate novel risk gene pathways.
    PLoS Genet. 2012;8(8):e1002843 PMID: 22912587
  67. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.
    Am J Hum Genet. 2005 Apr;76(4):572-80 PMID: 15706485
  68. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development.
    Development. 2004 Oct;131(20):5041-52 PMID: 15459098
  69. Characterization of TBX20 in human hearts and its regulation by TFAP2.
    J Cell Biochem. 2008 Jun 1;104(3):1022-33 PMID: 18275040
  70. New trends in chromosomal investigation in children with cardiovascular malformations.
    Cardiol Young. 2004 Dec;14(6):622-9 PMID: 15679998
  71. Williams-Beuren syndrome.
    N Engl J Med. 2010 Jan 21;362(3):239-52 PMID: 20089974
  72. Heart defects in X-linked heterotaxy: evidence for a genetic interaction of Zic3 with the nodal signaling pathway.
    Dev Dyn. 2006 Jun;235(6):1631-7 PMID: 16496285
  73. Abnormal cardiac conduction and morphogenesis in connexin40 and connexin43 double-deficient mice.
    Circ Res. 2000 Sep 1;87(5):399-405 PMID: 10969038
  74. X-linked situs abnormalities result from mutations in ZIC3.
    Nat Genet. 1997 Nov;17(3):305-8 PMID: 9354794
  75. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease.
    Cell. 2001 Sep 21;106(6):709-21 PMID: 11572777
  76. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation.
    Genes Dev. 2004 Jan 1;18(1):99-115 PMID: 14701881
  77. NOTCH2 mutations in Alagille syndrome.
    J Med Genet. 2012 Feb;49(2):138-44 PMID: 22209762
  78. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5.
    Nature. 2003 Jul 24;424(6947):443-7 PMID: 12845333
  79. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients.
    Am J Hum Genet. 1995 Jul;57(1):49-53 PMID: 7611295
  80. Gene prioritization through genomic data fusion.
    Nat Biotechnol. 2006 May;24(5):537-44 PMID: 16680138
  81. ACC/AHA 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease).
    Circulation. 2008 Dec 2;118(23):e714-833 PMID: 18997169
  82. Mutations in NOTCH1 cause aortic valve disease.
    Nature. 2005 Sep 8;437(7056):270-4 PMID: 16025100
  83. Differentiation, dedifferentiation, and apoptosis of smooth muscle cells during the development of the human ductus arteriosus.
    Arterioscler Thromb Vasc Biol. 1997 May;17(5):1003-9 PMID: 9157967
  84. Genetic variation of SAL-Like 4 (SALL4) in ventricular septal defect.
    Int J Cardiol. 2010 Nov 19;145(2):224-226 PMID: 19619907
  85. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.
    Am J Med Genet C Semin Med Genet. 2008 Nov 15;148C(4):246-51 PMID: 18932224
  86. Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies.
    Congenit Heart Dis. 2011 Nov-Dec;6(6):592-602 PMID: 22010865
  87. GATA4 mutations in 486 Chinese patients with congenital heart disease.
    Eur J Med Genet. 2008 Nov-Dec;51(6):527-35 PMID: 18672102
  88. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.
    Nat Genet. 2003 Aug;34(4):413-20 PMID: 12872123
  89. Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations.
    Hum Mol Genet. 2009 Mar 1;18(5):861-71 PMID: 19064609
  90. Sotos syndrome and haploinsufficiency of NSD1: clinical features of intragenic mutations and submicroscopic deletions.
    J Med Genet. 2003 Apr;40(4):285-9 PMID: 12676901
  91. Elastin: mutational spectrum in supravalvular aortic stenosis.
    Eur J Hum Genet. 2000 Dec;8(12):955-63 PMID: 11175284
  92. Retinoic acid down-regulates Tbx1 expression in vivo and in vitro.
    Dev Dyn. 2005 Apr;232(4):928-38 PMID: 15736167
  93. Clinical and molecular diagnosis of Miller-Dieker syndrome.
    Am J Hum Genet. 1991 Mar;48(3):584-94 PMID: 1671808
  94. Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats.
    Nature. 1993 Aug 19;364(6439):717-21 PMID: 8355785
  95. Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice.
    Curr Biol. 1998 Feb 26;8(5):299-302 PMID: 9501070
  96. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development.
    Development. 1999 Mar;126(6):1269-80 PMID: 10021345
  97. Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation.
    J Clin Invest. 2010 Oct;120(10):3493-507 PMID: 20890042
  98. Mutation in myosin heavy chain 6 causes atrial septal defect.
    Nat Genet. 2005 Apr;37(4):423-8 PMID: 15735645
  99. GATA4 transcription factor is required for ventral morphogenesis and heart tube formation.
    Genes Dev. 1997 Apr 15;11(8):1048-60 PMID: 9136932
  100. Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients.
    Eur Heart J. 2007 Nov;28(22):2778-84 PMID: 17384091
  101. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.
    J Med Genet. 1997 Oct;34(10):798-804 PMID: 9350810
  102. Familial transposition of the great arteries caused by multiple mutations in laterality genes.
    Heart. 2010 May;96(9):673-7 PMID: 19933292
  103. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis.
    Hepatology. 1999 Mar;29(3):822-9 PMID: 10051485
  104. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005.
    J Pediatr. 2008 Dec;153(6):807-13 PMID: 18657826
  105. Clinical characteristics and survival of trisomy 18 in a medical center in Taipei, 1988-2004.
    Am J Med Genet A. 2006 May 1;140(9):945-51 PMID: 16528742
  106. Two novel mutations of the IRX4 gene in patients with congenital heart disease.
    Hum Genet. 2011 Nov;130(5):657-62 PMID: 21544582
  107. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation.
    Cell. 2007 Mar 9;128(5):947-59 PMID: 17350578
  108. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes.
    N Engl J Med. 2008 Oct 16;359(16):1685-99 PMID: 18784092
  109. Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development.
    Development. 2004 Aug;131(16):3931-42 PMID: 15253934
  110. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.
    Curr Opin Genet Dev. 2009 Jun;19(3):230-6 PMID: 19467855
  111. Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development.
    Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14035-40 PMID: 22904188
  112. Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: early diagnosis of syndromic patients.
    Am J Med Genet A. 2012 Apr;158A(4):720-5 PMID: 22383218
  113. CHD7 cooperates with PBAF to control multipotent neural crest formation.
    Nature. 2010 Feb 18;463(7283):958-62 PMID: 20130577
  114. Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome.
    Am J Hum Genet. 2006 Aug;79(2):370-7 PMID: 16826528
  115. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.
    Cell. 2012 Apr 27;149(3):525-37 PMID: 22521361
  116. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.
    J Med Genet. 2006 Apr;43(4):306-14 PMID: 16155193
  117. Alpha-cardiac actin mutations produce atrial septal defects.
    Hum Mol Genet. 2008 Jan 15;17(2):256-65 PMID: 17947298
  118. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family.
    Am J Hum Genet. 2002 Nov;71(5):1195-9 PMID: 12395297
  119. Mutations in the sarcomere gene MYH7 in Ebstein anomaly.
    Circ Cardiovasc Genet. 2011 Feb;4(1):43-50 PMID: 21127202
  120. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.
    Nat Genet. 2004 Sep;36(9):955-7 PMID: 15300250
  121. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis.
    J Clin Invest. 2011 Apr;121(4):1585-95 PMID: 21364285
  122. A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations.
    Nat Genet. 2013 Jul;45(7):818-21 PMID: 23708190
  123. Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development.
    Dev Biol. 2009 Feb 15;326(2):368-77 PMID: 19084512
  124. Restricted distribution of connexin40, a gap junctional protein, in mammalian heart.
    Circ Res. 1994 May;74(5):839-51 PMID: 8156631
  125. 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 Jul;83(1):18-29 PMID: 18538293
  126. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway.
    Am J Hum Genet. 2006 Jul;79(1):169-73 PMID: 16773578
  127. Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate left-right axis determination.
    Dev Biol. 2005 Dec 1;288(1):1-20 PMID: 16289136
  128. Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions.
    Am J Hum Genet. 2007 Mar;80(3):510-7 PMID: 17273972
  129. Transcription factor pathways and congenital heart disease.
    Curr Top Dev Biol. 2012;100:253-77 PMID: 22449847
  130. 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 Nov;45(11):704-9 PMID: 18713793
  131. The MSL complex: X chromosome and beyond.
    Curr Opin Genet Dev. 2010 Apr;20(2):171-8 PMID: 20167472
  132. Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice.
    Dis Model Mech. 2009 May-Jun;2(5-6):283-94 PMID: 19383940
  133. Submicroscopic chromosomal copy number variations identified in children with hypoplastic left heart syndrome.
    Pediatr Cardiol. 2012 Jun;33(5):757-63 PMID: 22349727
  134. Epigenetics and cardiovascular development.
    Annu Rev Physiol. 2012;74:41-68 PMID: 22035349
  135. A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16.
    Mol Cell Biol. 2005 Nov;25(21):9175-88 PMID: 16227571
  136. Update on Kleefstra Syndrome.
    Mol Syndromol. 2012 Apr;2(3-5):202-212 PMID: 22670141
  137. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency.
    Development. 2002 Feb;129(4):1075-82 PMID: 11861489
  138. NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome.
    Am J Hum Genet. 2005 Dec;77(6):1092-101 PMID: 16380919
  139. Identification and functional analysis of CITED2 mutations in patients with congenital heart defects.
    Hum Mutat. 2005 Dec;26(6):575-82 PMID: 16287139
  140. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis.
    Genes Dev. 1997 Apr 15;11(8):1061-72 PMID: 9136933
  141. Mechanisms of T-box gene function in the developing heart.
    Cardiovasc Res. 2011 Jul 15;91(2):212-22 PMID: 21498422
  142. Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans.
    Am J Hum Genet. 2007 Nov;81(5):987-94 PMID: 17924340
  143. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.
    Nat Genet. 2008 Dec;40(12):1466-71 PMID: 19029900
  144. Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning.
    Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2915-20 PMID: 21282601
  145. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures.
    Nat Genet. 2008 Mar;40(3):322-8 PMID: 18278044
  146. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome.
    Clin Genet. 2012 Jun;81(6):542-54 PMID: 21457232
  147. Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating evidence from human genetics and model organisms.
    Hum Mol Genet. 2010 Apr 1;19(7):1286-301 PMID: 20071345
  148. Cryptic chromosomal abnormalities identified in children with congenital heart disease.
    Pediatr Res. 2008 Oct;64(4):358-63 PMID: 18535492
  149. Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract.
    Development. 2004 Jul;131(13):3217-27 PMID: 15175244
  150. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.
    Nat Genet. 2001 Dec;29(4):465-8 PMID: 11704759
  151. Common arterial trunk associated with a homeodomain mutation of NKX2.6.
    Hum Mol Genet. 2005 Mar 1;14(5):585-93 PMID: 15649947
  152. Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes.
    Am J Hum Genet. 1999 Jan;64(1):118-25 PMID: 9915950
  153. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation.
    Nat Genet. 2001 Jul;28(3):276-80 PMID: 11431700
  154. Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes.
    Genet Med. 2008 Apr;10(4):267-77 PMID: 18414210
  155. Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome.
    Hum Mutat. 2007 Nov;28(11):1098-107 PMID: 17565729
  156. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.
    Cell. 1998 Dec 11;95(6):829-37 PMID: 9865700
  157. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling.
    Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13933-8 PMID: 19666519
  158. The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear proteins in transcription.
    J Biol Chem. 2006 Jun 16;281(24):16264-71 PMID: 16603771
  159. Genetic abnormalities in FOXP1 are associated with congenital heart defects.
    Hum Mutat. 2013 Sep;34(9):1226-30 PMID: 23766104
  160. Dissecting spatio-temporal protein networks driving human heart development and related disorders.
    Mol Syst Biol. 2010 Jun 22;6:381 PMID: 20571530
  161. Novel arterial pathology in mice and humans hemizygous for elastin.
    J Clin Invest. 1998 Nov 15;102(10):1783-7 PMID: 9819363
  162. Identification of downstream genetic pathways of Tbx1 in the second heart field.
    Dev Biol. 2008 Apr 15;316(2):524-37 PMID: 18328475
  163. Improved national prevalence estimates for 18 selected major birth defects--United States, 1999-2001.
    MMWR Morb Mortal Wkly Rep. 2006 Jan 6;54(51):1301-5 PMID: 16397457
  164. Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease.
    Am J Hum Genet. 2012 Sep 7;91(3):489-501 PMID: 22939634
  165. Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.
    Nat Genet. 2001 Mar;27(3):293-8 PMID: 11242111
  166. Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls.
    Hum Mol Genet. 2012 Apr 1;21(7):1513-20 PMID: 22199024
  167. Alpha-cardiac myosin heavy chain (MYH6) mutations affecting myofibril formation are associated with congenital heart defects.
    Hum Mol Genet. 2010 Oct 15;19(20):4007-16 PMID: 20656787
  168. Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2.
    J Med Genet. 2005 Nov;42(11):871-6 PMID: 15831592
  169. The neural crest in cardiac congenital anomalies.
    Differentiation. 2012 Jul;84(1):25-40 PMID: 22595346
  170. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation.
    Curr Opin Cell Biol. 2008 Jun;20(3):341-8 PMID: 18508253
  171. Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome.
    Hum Mol Genet. 2005 Apr 15;14(8):983-95 PMID: 15746153
  172. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.
    Hum Mol Genet. 1997 Jul;6(7):1021-8 PMID: 9215670
  173. Subtelomeric deletions of chromosome 9q: a novel microdeletion syndrome.
    Am J Med Genet A. 2004 Aug 1;128A(4):340-51 PMID: 15264279
  174. Incidence of congenital heart disease: II. Prenatal incidence.
    Pediatr Cardiol. 1995 Jul-Aug;16(4):155-65 PMID: 7567659
  175. De novo mutations in histone-modifying genes in congenital heart disease.
    Nature. 2013 Jun 13;498(7453):220-3 PMID: 23665959
  176. Physical interaction between TBX5 and MEF2C is required for early heart development.
    Mol Cell Biol. 2009 Apr;29(8):2205-18 PMID: 19204083
  177. Insights into the pathogenesis and genetic background of patency of the ductus arteriosus.
    Neonatology. 2010 Jun;98(1):6-17 PMID: 19955832
  178. Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation.
    Eur J Med Genet. 2011 Mar-Apr;54(2):144-51 PMID: 21094706
  179. Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus.
    Nat Genet. 2000 May;25(1):42-6 PMID: 10802654
  180. Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
    Am J Med Genet A. 2011 Jul;155A(7):1511-6 PMID: 21671394
  181. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1.
    Hum Mol Genet. 1999 May;8(5):723-30 PMID: 10196361
  182. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development.
    Cell. 2007 Jun 29;129(7):1365-76 PMID: 17604724
  183. Determination of left-right patterning of the mouse embryo by artificial nodal flow.
    Nature. 2002 Jul 4;418(6893):96-9 PMID: 12097914
  184. The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs.
    PLoS Genet. 2011 Feb;7(2):e1001313 PMID: 21379568
  185. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.
    Nat Genet. 2012 Apr 29;44(6):639-41 PMID: 22544363
  186. Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease.
    J Mol Cell Cardiol. 2013 Jul;60:27-35 PMID: 23583836
  187. A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice.
    Development. 2002 May;129(9):2293-302 PMID: 11959836
  188. Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects.
    Hum Mol Genet. 2001 Oct 15;10(22):2549-56 PMID: 11709542
  189. Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype.
    Am J Hum Genet. 2010 Aug 13;87(2):250-7 PMID: 20619386
  190. Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
    Nat Genet. 2007 Aug;39(8):1013-7 PMID: 17603482
  191. Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot.
    Hum Mutat. 2003 Nov;22(5):372-7 PMID: 14517948
  192. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development.
    Dev Biol. 2001 Jul 1;235(1):62-73 PMID: 11412027
  193. Natural history of trisomy 18.
    Arch Dis Child Fetal Neonatal Ed. 1996 Jul;75(1):F38-41 PMID: 8795354
  194. Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.
    Am J Hum Genet. 2013 Jul 11;93(1):173-80 PMID: 23791108
  195. Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick.
    Hum Mol Genet. 2006 Dec 1;15(23):3394-410 PMID: 17047027
  196. Regulation of GATA4 transcriptional activity in cardiovascular development and disease.
    Curr Top Dev Biol. 2012;100:143-69 PMID: 22449843
  197. Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development.
    Dev Cell. 2010 Feb 16;18(2):275-87 PMID: 20159597
  198. Genotype-phenotype correlation in eight new patients with a deletion encompassing 2q31.1.
    Am J Med Genet A. 2010 May;152A(5):1213-24 PMID: 20425826
  199. Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer.
    Development. 1999 Jan;126(1):75-84 PMID: 9834187
  200. Cardiovascular manifestations in 75 patients with Williams syndrome.
    J Med Genet. 2002 Aug;39(8):554-8 PMID: 12161592
  201. The 11q terminal deletion disorder: a prospective study of 110 cases.
    Am J Med Genet A. 2004 Aug 15;129A(1):51-61 PMID: 15266616
  202. T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis.
    Development. 2005 May;132(10):2475-87 PMID: 15843407
  203. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.
    Am J Hum Genet. 1996 Oct;59(4):781-92 PMID: 8808592
  204. Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.
    Development. 2005 May;132(10):2451-62 PMID: 15843414
  205. Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16.
    Nat Genet. 2013 Jul;45(7):822-4 PMID: 23708191
  206. A novel atypical 22q11.2 distal deletion in father and son.
    J Med Genet. 2002 Oct;39(10):E62 PMID: 12362044
  207. Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia.
    Am J Med Genet A. 2009 Aug;149A(8):1661-77 PMID: 19606479
  208. Congenital heart disease in patients with Turner's syndrome. Italian Study Group for Turner Syndrome (ISGTS).
    J Pediatr. 1998 Nov;133(5):688-92 PMID: 9821430
  209. Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.
    Hum Mol Genet. 2013 Apr 1;22(7):1473-81 PMID: 23297363
  210. Rare copy number variants contribute to congenital left-sided heart disease.
    PLoS Genet. 2012 Sep;8(9):e1002903 PMID: 22969434
  211. Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes.
    Dev Cell. 2006 Jan;10(1):71-80 PMID: 16399079
  212. A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot.
    Hum Mutat. 2006 Mar;27(3):293-4 PMID: 16470721
  213. Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry.
    Cell. 1998 Aug 7;94(3):299-305 PMID: 9708732
  214. Natural history of trisomy 13.
    Arch Dis Child. 1994 Oct;71(4):343-5 PMID: 7979530
  215. Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.
    PLoS One. 2009 Jun 25;4(6):e6049 PMID: 19557177
  216. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.
    Nat Genet. 2001 Mar;27(3):286-91 PMID: 11242110
  217. Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum.
    Genet Med. 2006 Jul;8(7):417-27 PMID: 16845274
  218. The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene.
    Pediatrics. 2007 Jun;119(6):e1325-31 PMID: 17515436
  219. NPHP4 variants are associated with pleiotropic heart malformations.
    Circ Res. 2012 Jun 8;110(12):1564-74 PMID: 22550138
  220. Dominant-negative ALK2 allele associates with congenital heart defects.
    Circulation. 2009 Jun 23;119(24):3062-9 PMID: 19506109
  221. Germline mutations in HRAS proto-oncogene cause Costello syndrome.
    Nat Genet. 2005 Oct;37(10):1038-40 PMID: 16170316
  222. Array comparative genomic hybridization as a diagnostic tool for syndromic heart defects.
    J Pediatr. 2010 May;156(5):810-7, 817.e1-817.e4 PMID: 20138633
  223. Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome.
    J Med Genet. 2010 Mar;47(3):155-61 PMID: 19833603
  224. Discovery of a previously unrecognized microdeletion syndrome of 16p11.2-p12.2.
    Nat Genet. 2007 Sep;39(9):1071-3 PMID: 17704777
  225. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. [corrected]
    Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4006-11 PMID: 21330551
  226. Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB.
    Am J Med Genet. 1999 Jan 1;82(1):70-6 PMID: 9916847
  227. Foxh1 is essential for development of the anterior heart field.
    Dev Cell. 2004 Sep;7(3):331-45 PMID: 15363409
  228. Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation.
    Pediatrics. 2008 Feb;121(2):404-10 PMID: 18245432
  229. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system.
    J Clin Invest. 2004 Apr;113(8):1130-7 PMID: 15085192
  230. Congenital heart disease-causing Gata4 mutation displays functional deficits in vivo.
    PLoS Genet. 2012;8(5):e1002690 PMID: 22589735
  231. tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila.
    Genes Dev. 1993 Jul;7(7B):1325-40 PMID: 8101173
  232. The left-right axis in the mouse: from origin to morphology.
    Development. 2006 Jun;133(11):2095-104 PMID: 16672339
  233. Identification of GATA6 sequence variants in patients with congenital heart defects.
    Pediatr Res. 2010 Oct;68(4):281-5 PMID: 20581743
  234. Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1.
    Dev Biol. 2005 Sep 15;285(2):554-69 PMID: 16109395
  235. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
    Nat Genet. 2010 Sep;42(9):790-3 PMID: 20711175
  236. Germline gain-of-function mutations in SOS1 cause Noonan syndrome.
    Nat Genet. 2007 Jan;39(1):70-4 PMID: 17143285
  237. Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.
    PLoS Genet. 2013;9(1):e1003109 PMID: 23358434
  238. Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome.
    J Med Genet. 2005 Apr;42(4):299-306 PMID: 15805155
  239. Potocki-Lupski syndrome: a microduplication syndrome associated with oropharyngeal dysphagia and failure to thrive.
    J Pediatr. 2011 Apr;158(4):655-659.e2 PMID: 21168152
  240. De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot.
    Nat Genet. 2009 Aug;41(8):931-5 PMID: 19597493
  241. The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors.
    EMBO J. 1997 Sep 15;16(18):5687-96 PMID: 9312027
  242. Loss of Cited2 causes congenital heart disease by perturbing left-right patterning of the body axis.
    Hum Mol Genet. 2011 Mar 15;20(6):1097-110 PMID: 21224256
  243. MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development.
    Hum Mol Genet. 2013 Nov 1;22(21):4339-48 PMID: 23773997
  244. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block.
    Cell. 2004 Apr 30;117(3):373-86 PMID: 15109497
  245. Microduplication 22q11.2: a new chromosomal syndrome.
    Eur J Med Genet. 2009 Mar-Jun;52(2-3):88-93 PMID: 19254783
  246. Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer.
    Genes Dev. 2003 Jan 15;17(2):269-81 PMID: 12533514
  247. Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus.
    Genet Test. 2008 Sep;12(3):457-9 PMID: 18752453
  248. Zic3 is required in the migrating primitive streak for node morphogenesis and left-right patterning.
    Hum Mol Genet. 2013 May 15;22(10):1913-23 PMID: 23303524
  249. Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects.
    Am J Hum Genet. 2003 Apr;72(4):1047-52 PMID: 12632326
  250. Cardiac alpha-myosin (MYH6) is the predominant sarcomeric disease gene for familial atrial septal defects.
    PLoS One. 2011;6(12):e28872 PMID: 22194935
  251. 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. 2007 Aug;81(2):280-91 PMID: 17668378
  252. Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2.
    Development. 2005 Jun;132(12):2697-707 PMID: 15901664
  253. Familial nonsyndromic patent ductus arteriosus caused by mutations in TFAP2B.
    Pediatr Cardiol. 2011 Oct;32(7):958-65 PMID: 21643846
  254. A GATA-dependent right ventricular enhancer controls dHAND transcription in the developing heart.
    Development. 2000 Dec;127(24):5331-41 PMID: 11076755
  255. Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome.
    Nat Genet. 1997 Jan;15(1):30-5 PMID: 8988165
  256. Genetic counseling for the 22q11.2 deletion.
    Dev Disabil Res Rev. 2008;14(1):69-74 PMID: 18636638
  257. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.
    Genes Dev. 2005 Apr 1;19(7):815-26 PMID: 15774718
  258. Two populations of node monocilia initiate left-right asymmetry in the mouse.
    Cell. 2003 Jul 11;114(1):61-73 PMID: 12859898
  259. Linkage analysis of left ventricular outflow tract malformations (aortic valve stenosis, coarctation of the aorta, and hypoplastic left heart syndrome).
    Eur J Hum Genet. 2009 Jun;17(6):811-9 PMID: 19142209
  260. Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2.
    J Biol Chem. 2002 Mar 8;277(10):8559-65 PMID: 11744733
  261. A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice.
    Development. 1998 Nov;125(22):4461-70 PMID: 9778505
  262. New developments in the second heart field.
    Differentiation. 2012 Jul;84(1):17-24 PMID: 22521611
  263. Missense mutations and gene interruption in PROSIT240, a novel TRAP240-like gene, in patients with congenital heart defect (transposition of the great arteries).
    Circulation. 2003 Dec 9;108(23):2843-50 PMID: 14638541
  264. Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns.
    Genome Res. 2009 Apr;19(4):590-601 PMID: 19251738
  265. Identification of a recurrent microdeletion at 17q23.1q23.2 flanked by segmental duplications associated with heart defects and limb abnormalities.
    Am J Hum Genet. 2010 Mar 12;86(3):454-61 PMID: 20206336
  266. The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci.
    Nat Cell Biol. 2004 Dec;6(12):1236-44 PMID: 15543136
  267. Myocardial Tbx20 regulates early atrioventricular canal formation and endocardial epithelial-mesenchymal transition via Bmp2.
    Dev Biol. 2011 Dec 15;360(2):381-90 PMID: 21983003
  268. Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development.
    Development. 2005 Mar;132(6):1337-48 PMID: 15750185
  269. Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF).
    Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9280-5 PMID: 19470456
  270. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.
    Am J Hum Genet. 2005 Aug;77(2):193-204 PMID: 15942875
  271. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems.
    Am J Hum Genet. 2010 Aug 13;87(2):219-28 PMID: 20691407
  272. Phenotypic manifestations of copy number variation in chromosome 16p13.11.
    Eur J Hum Genet. 2011 Mar;19(3):280-6 PMID: 21150890
  273. Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation.
    Hum Mutat. 2012 Apr;33(4):720-7 PMID: 22275001
  274. Role of TBX1 in human del22q11.2 syndrome.
    Lancet. 2003 Oct 25;362(9393):1366-73 PMID: 14585638
  275. Challenges of interpreting copy number variation in syndromic and non-syndromic congenital heart defects.
    Cytogenet Genome Res. 2011;135(3-4):251-9 PMID: 21921585
  276. A genetic link between Tbx1 and fibroblast growth factor signaling.
    Development. 2002 Oct;129(19):4605-11 PMID: 12223416
  277. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome.
    J Med Genet. 2009 Aug;46(8):511-23 PMID: 19372089
  278. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2.
    J Biol Chem. 2003 May 2;278(18):16021-9 PMID: 12586840
  279. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
    J Med Genet. 2008 Nov;45(11):710-20 PMID: 18628315
  280. Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype.
    Nat Genet. 2012 Apr 29;44(6):636-8 PMID: 22544367
  281. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.
    Nature. 1995 Jul 27;376(6538):348-51 PMID: 7630403
  282. Heterogeneity of genetic modifiers ensures normal cardiac development.
    Circulation. 2010 Mar 23;121(11):1313-21 PMID: 20212279
  283. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3.
    Am J Hum Genet. 2003 Apr;72(4):918-30 PMID: 12621583
  284. Spectrum of heart disease associated with murine and human GATA4 mutation.
    J Mol Cell Cardiol. 2007 Dec;43(6):677-85 PMID: 17643447
  285. X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3.
    Eur J Hum Genet. 2000 Sep;8(9):704-8 PMID: 10980576
  286. Haploinsufficiency of TAB2 causes congenital heart defects in humans.
    Am J Hum Genet. 2010 Jun 11;86(6):839-49 PMID: 20493459
  287. Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project.
    Genet Med. 2008 Mar;10(3):173-80 PMID: 18344706
  288. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation.
    Am J Hum Genet. 2006 Feb;78(2):303-14 PMID: 16400610
Article Info
Journal
Cellular and molecular life sciences : CMLS
Abbr.
Cell Mol Life Sci
ISSN
1420-9071
DOI
10.1007/s00018-013-1430-1
Published
2014-04-00
Epub
2013-00-10
Pages
1327-52
Language
English
Region
Switzerland
NLM ID
9705402
PMCID
PMC3958813
Subset
IM
External Links
PubMed source DOI: 10.1007/s00018-013-1430-1 PMC Full Text View journal details
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