NKX2.5 and congenital heart defects: A population-based study

Hobbs, Charlotte A.; Cleves, Mario A.; Keith, Carmen; Ghaffar, Sadia; James, S. Jill

doi:10.1002/ajmg.a.30509

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…A number of missense and nonsense mutations in NKX2.5 have been found in families with inherited autosomaldominant ASD and atrioventricular conduction block (Table 6; Akcaboy et al 2008;Benson et al 1999;Ding et al 2009;Elliott et al 2003;Esposito et al 2009;GioliPereira et al 2010;Goldmuntz et al 2001;GutierrezRoelens et al 2002;Hobbs et al 2005;Hosoda et al 1999;Ikeda et al 2002;Liu et al 2009a, b;McElhinney et al 2003;Schott et al 1998;Stallmeyer et al 2010;Watanabe et al 2002;Zhang et al 2009a, b). Other congenital heart abnormalities have been observed at low penetrance in these families, including VSD, Ebstein's anomaly, TOF, subvalvular aortic stenosis, and tricuspid valve abnormality.…”

Section: Discussionmentioning

confidence: 95%

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease

et al. 2010

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A number of mutations in GATA4 and NKX2.5 have been identified to be causative for a subset of familial congenital heart defects (CHDs) and a small number of sporadic CHDs. In this study, we evaluated common GATA4 and NKX2.5 mutations in 135 Chinese pediatric patients with non-familial congenital heart defects. Two novel mutations in the coding region of GATA4 were identified, namely, 487C >T (Pro163Ser) in exon 1 in a child with tetralogy of Fallot and 1220C >A (Pro407Gln) in exon 6 in a pediatric patient with outlet membranous ventricular septal defect. We also found 848C >A (Pro283Gln) in exon 2 of the NKX2.5 gene in a pediatric patient with ventricular septal defect, patent ductus arteriosus and aortic isthmus stenosis. None of the mutations was detected in healthy control subjects (n = 114). This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted.

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Section: Discussionmentioning

confidence: 95%

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease

et al. 2010

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“…However, most genetic studies of nonsyndromic birth defects continue to rely on candidate SNPs, leaving most of the genome unexplored. 34,35 Thus, there is a need to comprehensively explore the genome to identify new regions harboring genes associated with birth defects. 36 In addition to SNPs, which affect only a single nucleotide base, multiple lines of evidence indicate that copy number variants (CNVs) can play an important role in the etiology of some cases of birth defects.…”

Section: Genome Wide Association Studies (Gwas) and Copy Number Variamentioning

confidence: 99%

Genetic Epidemiology and Nonsyndromic Structural Birth Defects

et al. 2014

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Birth defects are a leading cause of infant morbidity and mortality worldwide. The vast majority of birth defects are nonsyndromic, and although their etiologies remain mostly unknown, evidence supports the hypothesis that they result from the complex interaction of genetic, epigenetic, environmental, and lifestyle factors. Since our last review published in 2002 describing the basic tools of genetic epidemiology used to study nonsyndromic structural birth defects, many new approaches have become available and have been used with varying success. Through rapid advances in genomic technologies, investigators are now able to interrogate large portions of the genome at a fraction of previous costs. With next generation sequencing (NGS), research has progressed from assessing a small percentage of single nucleotide polymorphisms (SNPs) to assessing the entire human protein-coding repertoire (exome) – an approach that is starting to uncover rare but informative mutations associated with nonsyndromic birth defects. Here we report on the current state of genetic epidemiology of birth defects and comment on future challenges and opportunities. We consider issues of study design, and we discuss common variant approaches including candidate gene studies and genome-wide association studies (GWAS). We also discuss the complexities embedded in exploring gene-environment interactions. We complete our review by describing new and promising NGS technologies and examining how the study of epigenetic mechanisms could become the key to unraveling the complex etiologies of nonsyndromic structural birth defects.

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“…10 11 18 19 In certain cases (mainly in kindreds with mutations in the homeobox or 3′ coding region of the gene), progressive heart block is seen alongside the ASD,11 17 20 suggesting a need for sustained NKX2.5 input to maintain the adult cardiac conduction system. This view is backed by data from animal models.…”

Section: Nkx25 Mutationsmentioning

confidence: 99%

“…Although families with Mendelian CHD make up a very small proportion of the total CHD burden in the general population, the genes that have been identified in these kindreds are the subject of intensive study. In particular, there is great interest in ascertaining the extent to which de novo mutations or genetic variants of these genes contribute to the risk of “common” “sporadic” forms of congenital heart defect 10 11 . w7 …”

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confidence: 99%

Fresh fields and pathways new: recent genetic insights into cardiac malformation

Leong

Freeman

Keavney

2009

Heart

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Cardiovascular malformations are the most common type of birth defect. Currently, only a fraction of cases have associated causative factors and little is known about the aetiology of the rest. Despite this, our understanding of normal and abnormal heart development continues to grow, a number of recent discoveries even challenging long-held concepts. In this review, we highlight some of this new knowledge, emphasising aspects that may be of interest to the clinician.

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NKX2.5 and congenital heart defects: A population-based study

Cited by 15 publications

References 23 publications

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease

Genetic Epidemiology and Nonsyndromic Structural Birth Defects

Fresh fields and pathways new: recent genetic insights into cardiac malformation

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