Genetics and Genomics of Congenital Heart Disease

Zaidi, Samir; Brueckner, Martina

doi:10.1161/circresaha.116.309140

Cited by 396 publications

(468 citation statements)

References 152 publications

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“…Epigenetics play a nonignorable role in fetal development. It has been reported that histone methylation plays important roles in cardiac lineage specification and differentiation [25], heart development [5,26], and the pathogenesis of congenital and adult heart diseases [2,27,28]. Histone deacetylase activity controls valvulogenesis in zebrafish by promoting myocardial expression of Bmp4 at the atrioventricular boundary [29].…”

Section: Discussionmentioning

confidence: 99%

“…CHD can be divided into nonsyndromic phenotypes, including gene mutations, and syndromic phenotypes, including chromosomal abnormalities, such as Down's syndrome, Edwards syndrome, and Patau syndrome. Only about one-third of CHD cases have been described as clear genetic or chromosomal abnormality cases [2,3]. The causes of CHD are complex and involve interaction among the environment, genetics, and epigenetics.…”

Section: Introductionmentioning

confidence: 99%

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Decreased Amino Acid Concentrations are Involved in Congenital Heart Disease

Lai

Zhang

et al. 2019

Ann Nutr Metab

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Objective: Congenital heart disease (CHD) is the most common malformation in China. In this study, we determined whether amino acids (AAs) in the amniotic fluid (AF) of patients with CHD changed and clarified whether AAs would affect the insulin-like growth factor type 1 receptor (IGF1R). Method: Fifty-seven AF samples from pregnant women carrying CHD-aﬀected (n = 17) or normal (n = 40) fetuses were collected. The AA concentrations were measured in AF by liquid chromatography-tandem mass spectrometry. The IGF axis-related and epigenetic marker proteins in AF after serial treatments were quantified using a multiple reaction monitoring approach. IGF1R and P300 were also confirmed by Western blot in AF without any treatment. Results: Most AAs decreased in the AF of patients with CHD. P300 and IGF1R decreased significantly in the CHD group. When H9C2 cells were cultured in one-half AA concentrations, the expression of P300 and IGF1R was reduced. Histone acetylation of the IGF1R promoter also decreased. Conclusion: Our data suggest that AAs decreased in the AF of patients with CHD. AAs may partly regulate the IGF1R through P300, which may be involved in heart development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decreased Amino Acid Concentrations are Involved in Congenital Heart Disease

Lai

Zhang

et al. 2019

Ann Nutr Metab

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“…In general, de novo mutations are more deleterious and cause more significant comorbidities than the mutations seen in Mendelian CHD (43). De novo mutations primarily cause CHD by altering critical developmental pathways shared by multiple developing organ systems, such as: chromatin remodeling (a critical process for regulating gene expression) and Notch signaling (instrumental for local intercellular communication in a variety of organ systems), (11, 44–48). The next section will show that mutations affecting these pathways provide a genetic explanation not only of CHD but also for the of some of the comorbidities that affect long term outcomes in CHD patients.…”

Section: The Genetics Of Chdmentioning

confidence: 99%

“…Figure 2 presents an algorithm for clinicians to use when beginning a genetics evaluation of a CHD patient (11). The key to efficient and appropriate testing of CHD patients is the clinical context of the patient.…”

Section: Genetic Testing In Chd Patientsmentioning

confidence: 99%

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The genetics of congenital heart disease… understanding and improving long-term outcomes in congenital heart disease: a review for the general cardiologist and primary care physician

Simmons¹,

Brueckner²

2017

Current Opinion in Pediatrics

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Purpose of the Review This review has two purposes: 1) To provide an updated review of the genetic causes of congenital heart disease (CHD) and the clinical implications of these genetic mutations; 2) To provide a clinical algorithm for clinicians considering a genetics evaluation of a CHD patient. Recent Findings A large portion of congenital heart disease is thought to have a significant genetic contribution, and at this time a genetic cause can be identified in approximately 35% of patients. Through the advances made possible by next generation sequencing, many of the comorbidities that are frequently seen in patients with genetic congenital heart disease patients can be attributed to the genetic mutation that caused the congenital heart disease. These comorbidities are both cardiac and non-cardiac and include: neurodevelopmental disability, pulmonary disease, heart failure, renal dysfunction, arrhythmia and an increased risk of malignancy. Identification of the genetic cause of congenital heart disease helps reduce patient morbidity and mortality by improving preventive and early intervention therapies to address these comorbidities. Summary Through an understanding of the clinical implications of the genetic underpinning of congenital heart disease, clinicians can provide care tailored to an individual patient and continue to improve the outcomes of congenital heart disease patients.

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Genetics of Human Congenital Heart Disease

Wilsdon

2018

Encyclopedia of Life Sciences

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Congenital heart disease (CHD) affects 0.9% of babies born in the United Kingdom. With improvements in medical and surgical treatments, individuals are surviving longer, and there are now more adults surviving with CHD than children. Prospective parents may ask about the chances of any children they have being affected. Unfortunately, the rate of genetic diagnosis in CHD is relatively low. CHD is likely to result from a complex interaction of genes and the environment. Recent sequencing studies in large cohorts of individuals with CHD have started to decipher the genetic contribution. There is a role for de novo and inherited mutations in CHD, in addition to chromosomal abnormalities, copy number variation, somatic mutations and epigenetics. Whole exome sequencing studies have identified novel CHD genes and expanded the phenotype of known CHD genes, but researchers and clinicians must also consider how to deal with secondary findings which are unrelated to the primary research aim. Key Concepts Congenital heart disease is the most common birth defect. Some individuals have complex health needs requiring lifelong follow‐up. Mendelian inheritance is rare in CHD, and it is likely that CHD results from a complex interaction between genes and the environment. Reduced penetrance and variable expressivity are common in CHD. Most individuals have CHD in isolation (nonsyndromic CHD). Syndromic CHD affects a smaller proportion of people, and is the combination of CHD with another extracardiac congenital abnormality and/or neurodevelopmental disability. A genetic diagnosis is more likely to be identified in syndromic CHD, but the majority of individuals have nonsyndromic CHD. Untargeted sequencing in large cohorts with CHD can identify novel genes and expand the phenotypic spectrum of known genes. There may be a shared pathogenesis between CHD and neurodevelopmental disability. Collaboration between researchers will be required to fully understand the genetic causes of CHD. Sequencing will generate secondary findings that are not related to the primary aim of the research. Clinicians and researchers have a duty of care to their research participants and should consider the methods to deal with these.

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Genetics and Genomics of Congenital Heart Disease

Cited by 396 publications

References 152 publications

Decreased Amino Acid Concentrations are Involved in Congenital Heart Disease

Decreased Amino Acid Concentrations are Involved in Congenital Heart Disease

The genetics of congenital heart disease… understanding and improving long-term outcomes in congenital heart disease: a review for the general cardiologist and primary care physician

Genetics of Human Congenital Heart Disease

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