scholarly journals Congenitalis vitiumok genetikai heterogenitása és komplexitása

2018 ◽  
Vol 159 (17) ◽  
pp. 661-670
Author(s):  
Dóra Nagy ◽  
Márta Széll
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Developmental Disorders ◽  
Isolated Heart ◽  
Heart Defects ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Reproductive Age ◽  
Number Of Patients ◽  
Monogenic Diseases

Abstract: Congenital heart defects are the most common birth defects, they account for approximately one third of all cases. They are clinically heterogeneous, vary widely in severity, treatability and prognosis and may occur as part of multiple developmental disorders, such as chromosome aberrations, microdeletion syndromes and monogenic diseases, or as isolated defects. Syndromic forms account for 25–40%, isolated forms for 60–75% of all cases. With conventional cytogenetic and next-generation molecular genetic methods, numerous genetic alterations have been identified in evolutionarily highly conserved genes of transcriptional regulators, signaling molecules and structural proteins, which are critical to normal cardiogenesis, mostly in cases with syndromic congenital heart defects. On the other hand, the genetic cause can be detected only in around 11% of isolated heart defects. The survival rate and life quality of patients with congenital heart defects have improved significantly in the last decades thanks to the remarkable development of prenatal, postnatal diagnostics as well as of heart and thoracic surgery of cardiovascular diseases. Since the number of patients, living into adulthood and reproductive age, is constantly increasing, the better understanding of the genetics of congenital heart defects may be crucial for the diagnosis, prognosis and positive family planning of patients. Orv Hetil. 2018; 159(17): 661–670.

scholarly journals Epigenomic and Transcriptomic Dynamics During Human Heart Organogenesis

2020 ◽  
Vol 127 (9) ◽  
Author(s):  
Jennifer VanOudenhove ◽  
Tara N. Yankee ◽  
Andrea Wilderman ◽  
Justin Cotney
Keyword(s):  
Gene Expression ◽  
Congenital Heart Defects ◽  
Human Heart ◽  
Congenital Heart ◽  
Heart Defects ◽  
Regulatory Control ◽  
Whole Genome Sequencing Data ◽  
Regulatory Sequences ◽  
Sequencing Data ◽  
Number Of Patients

Rationale: There is growing evidence that common variants and rare sequence alterations in regulatory sequences can result in birth defects or predisposition to disease. Congenital heart defects are the most common birth defect and have a clear genetic component, yet only a third of cases can be attributed to structural variation in the genome or a mutation in a gene. The remaining unknown cases could be caused by alterations in regulatory sequences. Objective: Identify regulatory sequences and gene expression networks that are active during organogenesis of the human heart. Determine whether these sites and networks are enriched for disease-relevant genes and associated genetic variation. Methods and Results: We characterized ChromHMM (chromatin state) and gene expression dynamics during human heart organogenesis. We profiled 7 histone modifications in embryonic hearts from each of 9 distinct Carnegie stages (13–14, 16–21, and 23), annotated chromatin states, and compared these maps to over 100 human tissues and cell types. We also generated RNA-sequencing data, performed differential expression, and constructed weighted gene coexpression networks. We identified 177 412 heart enhancers; 12 395 had not been previously annotated as strong enhancers. We identified 92% of all functionally validated heart-positive enhancers (n=281; 7.5× enrichment; P <2.2×10 −16 ). Integration of these data demonstrated novel heart enhancers are enriched near genes expressed more strongly in cardiac tissue and are enriched for variants associated with ECG measures and atrial fibrillation. Our gene expression network analysis identified gene modules strongly enriched for heart-related functions, regulatory control by heart-specific enhancers, and putative disease genes. Conclusions: Well-connected hub genes with heart-specific expression targeted by embryonic heart-specific enhancers are likely disease candidates. Our functional annotations will allow for better interpretation of whole genome sequencing data in the large number of patients affected by congenital heart defects.

scholarly journals Pulmonary hypertension in infants with congenital heart defects: are leukotrienes involved?

1997 ◽  
Vol 6 (5-6) ◽  
pp. 323-326 ◽  
Author(s):  
A. Serraf ◽  
J-P. Gascard ◽  
J. Bruniaux ◽  
C. Labat ◽  
C. Planche ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Congenital Heart Defects ◽  
Pulmonary Blood Flow ◽  
Congenital Heart ◽  
Heart Defects ◽  
Blood Levels ◽  
Blood Samples ◽  
Number Of Patients ◽  
Pulmonary Arterial

The circulating levels of leukotriene E4in infants with congenital heart defects, increased pulmonary blood flow and pulmonary arterial hypertension, were determined and compared with infants with decreased pulmonary blood flow (Tetralogy of Fallot). There was no correlation (r=0.38) between the pulmonary arterial pressure (56 ± 4 mmHg) and the leukotriene E4levels (1.37 ± 0.67 ng/ml blood) measured in peripheral blood samples from the hypertensive group prior to surgery. There was considerable variation in the detectable leukotriene E4levels in blood samples from different patients. The levels detected in the blood samples between the two groups of patients was similar. These data suggest that neither the surgical repair during cardiopulmonary bypass nor the pulmonary hypertension appeared to modify the leukotriene E4blood levels in the small number of patients studied.

scholarly journals Сongenital diseases of the heart among newborn children: genetic aspects

2019 ◽  
Keyword(s):  
Pregnant Women ◽  
Birth Defects ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Heart Defects ◽  
Circulatory System ◽  
Reproductive Age ◽  
Multiple Birth ◽  
Perinatal Pathology

Congenital heart defects are a heterogeneous group of diseases that occur as isolation or a part of multiple birth defects, gene disorders or chromosomal abnormalities. Chromosomal abnormalities and its underlying syndromes are the cause of 6 to 36% of cases of congenital heart defects. Monogenic etiology is proven in about 8% of cases, and the main group - about 90% of the congenital heart defects is the result of an unfavorable combination of genetic predisposition and external factors. The causes of early neonatal infant mortality are dominated by incompatible birth defects: almost 26% of perinatal and neonatal deaths are associated with congenital child pathology. Heart defects compose about 30% of all birth defects. They rank first place among the diseases that lead to perinatal mortality and early disability. World statistics show that the incidence of birth defects in the world is 9 per 1000 newborns, in Europe - 8/1000, which is 4 times more frequent than neural tube defects and 6 times higher than chromosomal abnormalities. In Ukraine, about 5,000 children with congenital heart defects are born each year, and the total number of those children on dispensary records reaches more than 45,000. Knowledge about the prevalence of birth defects in the region is needed to develop new information markers of the risk of congenital pathology of the circulatory system for women of reproductive age. Data on the incidence of congenital heart defects of fetuses and newborns in the region will allow the creation of a database for follow-up studies, which will facilitate the timely identification of pregnant women at risk. This will improve the prognosis of pregnancy, reduce the level of perinatal pathology, which will have a significant medical and social effect. The data obtained will allow to create preconditions for improvement of approaches to the definition of risk groups of perinatal pathology, perfection of specialized care for pregnant women with risk of congenital heart defects of the fetus.

Structural diseases of the heart: genetics of congenital heart diseases

ESC CardioMed ◽  
2018 ◽  
pp. 716-719
Author(s):  
Daniela Q. C. M. Barge-Schaapveld ◽  
Marco C. DeRuiter ◽  
Conny C. van Munsteren ◽  
Monique R. M. Jongbloed
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Reproductive Age ◽  
Congenital Defects ◽  
Clinical Genetics ◽  
Incomplete Penetrance ◽  
Number Of Patients ◽  
The Impact ◽  
Practical Recommendations

Congenital heart defects are the most common congenital defects. As a substantial number of patients with congenital heart disease (CHD) now reach reproductive age, the cardiologist dealing with grown-up patients with CHD is confronted with questions from patients regarding the impact of their CHD on pregnancy and offspring, and genetic counselling is becoming more relevant to clinical practice. Developments in the field of clinical genetics do not always facilitate clinicians’ knowledge and reasoning. Interpretation of the often large DNA datasets is challenging, especially in the light of phenotypic heterogeneity and incomplete penetrance, and requires specific expertise. In this chapter, the genetics of CHD are addressed. An overview of ‘causative’ genes is provided, that is, genes with a high likelihood to be involved in the development of human CHD and found so far to harbour (likely) pathogenic mutations in patients. In addition, the challenges and limitations in determining such genes are addressed and pitfalls in interpreting DNA variants in these genes discussed. The fact that single genes may in some instances be associated with different forms of CHD, may be explained by the broad range of cellular contributions during embryology, which will be briefly addressed. Finally, practical recommendations in addressing the genetics of CHD are provided.

scholarly journals Congenital Anomalies of the Kidney and Urinary Tract in Children with Congenital Heart Defects

2020 ◽  
Vol 45 (2) ◽  
pp. 307-313
Author(s):  
Dapeng Jiang ◽  
Qi Wang ◽  
Zhengzhou Shi ◽  
Jie Sun
Keyword(s):  
Urinary Tract ◽  
Congenital Heart Defects ◽  
Congenital Anomalies ◽  
Congenital Heart ◽  
Medical Center ◽  
Heart Defects ◽  
Clinical Manifestations ◽  
Number Of Patients ◽  
Significant Difference ◽  
History Of

Background/Aims: To investigate the incidence and clinical characteristics of congenital anomalies of the kidney and urinary tract (CAKUT) in children with congenital heart defects (CHD). Methods: We retrospectively analyzed the clinical data of children with CHD with CAKUT admitted to the Shanghai Children’s Medical Center affiliated with the Shanghai Jiao Tong University School of Medicine between September 2018 and March 2019. Patients underwent routine examinations for liver, kidney, and coagulation function, and urinary tract ultrasonography, and we summarized patients’ clinical manifestations and imaging abnormalities. Results: A total of 1,410 children with CHD were diagnosed and treated in our hospital. The total number of patients with abnormal urogenital systems was 104, and hydronephrosis was the most common abnormality, followed by vesicoureteral reflux and duplication of the kidney and ureter. The overall prevalence of CAKUT was 7.4%. There was no statistically significant difference for maternal age, sex, parity, gestational age, and history of medication during pregnancy between the patients with CAKUT and those without CAKUT. Conclusion: The incidence of CAKUT in our patients with CHD was significantly higher than that in the general population. We recommend urinary ultrasonography as a routine examination for children with CHD for early detection of CAKUT, to avoid missed diagnoses, and to initiate appropriate treatment.

scholarly journals Estimate the Frequency of Causal Genetic Variants in Fetuses With Congenital Heart Defects: a Chinese Cohort Study

2021 ◽  
Author(s):  
Fengying Lu ◽  
Peng Xue ◽  
Bin Zhang ◽  
Jing Wang ◽  
Jianbin Liu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Chromosomal Abnormalities ◽  
Diagnostic Yield ◽  
Hot Spot ◽  
Isolated Heart ◽  
Heart Defects ◽  
Copy Number Variations ◽  
Considerable Proportion

Abstract Purpose: This cohort study was designed to assess the prevalence of chromosomal abnormalities in fetuses with different types of congenital heart defects (CHD).Methods: In a cohort of 200 fetuses with CHD, we performed prenatal chromosome microarray analysis (CMA) firstly, and then WES analysis was carried out on some fetuses with negative CMA results. Meanwhile, we conducted a systematic literature search on hot spot pathogenic copy number variations (CNVs) related to CHD in the Chinese population.Results: Chromosomal abnormalities were detected in 49 (24.5%) fetuses after prenatal CMA detection, including 23(11.5%) with aneuploidies and 26 (13.0%) with significant clinical CNVs. The additional diagnostic yield diagnosed by followed WES was 11.5% (6/52). The incidence of total chromosomal abnormality in the non-isolated CHD group (31.8%) was higher than that in the isolated CHD group (20.9%), mainly because the incidence of aneuploidy was significantly increased when CHD combined with extracardial structural abnormalities or soft markers. The chromosome abnormal rate of complex CHD group was higher than that of the simple CHD group, but the difference was not statistically significant (31.8% vs. 23.6%, P = 0.398). The most common CNVs detected in CHD fetuses was the 22q11.2 deletions, followed by deletions of 5p15.33p15.31, deletions of 15q13.2q13.3, deletions of 11q24.2q25, deletions of 17p13.3p13.2, duplications of 17q12.Conclusion: CMA is the recommended initial examination for cases of CHD in the prenatal setting, whether it is simple heart defects or isolated heart defect. For cases with negative CMA results, the follow-up application of WES will offer a considerable proportion of additional detection of clinical significance.

scholarly journals Perspectives in the management of congenital heart defects in adult patients

2015 ◽  
Vol 156 (3) ◽  
pp. 92-97
Author(s):  
István Hartyánszky ◽  
Sándor Varga ◽  
Kálmán Havasi ◽  
Barna Babik ◽  
Márta Katona ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Adult Patients ◽  
Univentricular Heart ◽  
Transposition Of Great Arteries ◽  
Number Of Patients

Due to improving results in congenital heart surgery, the number of adult patients with congenital heart defect is increasing. The question is: what kind of problems can be managed in this patient-group? The authors review the different problems of management of congenital heart defects in adults based on national and international literature data. Simple defects recognised in adults, postoperative residual problems, changing of small grafts and valves, correction of primary or operated coarctation aortae can be usually managed without problems. A very close follow-up is necessary to establish the correct period for heart transplantation in patients with transposition of great arteries with Senning/Mustard operation, and univentricular heart corrected with “Fontan-circulation” type surgical procedure. The authors conclude that although the number of patients increases, only a few congenital heart diseases may cause problems. It seems important (1) to monitor asymptomatic patient who underwent operation (Fallot-IV, Ross procedure, etc.), (2) follow up regularly patients who underwent Senning/Mustard procedure (magnetic resonance imaging, echocardiography, brain natriuretic peptide measurement), (3) define the proper period of preparation for heart transplantation of patients with a univentricular heart, with special attention to the possibility of multiorgan (lung, liver, etc.) failure. Due to the improvement of foetal diagnosis of congenital heart defects, the number of patients with complex congenital heart defects is decreasing. The standard management of these patients could be primary heart transplantation in infancy. Orv. Hetil., 2015, 156(3), 92–97.

Genetics of CV diseases

ESC CardioMed ◽  
2018 ◽  
pp. 716-719
Author(s):  
Daniela Q.C.M. Barge-Schaapveld ◽  
Marco C. DeRuiter ◽  
Conny C. van Munsteren ◽  
Monique R.M. Jongbloed
Keyword(s):  
Congenital Heart ◽  
Heart Defects ◽  
Reproductive Age ◽  
Congenital Defects ◽  
Clinical Genetics ◽  
Incomplete Penetrance ◽  
High Likelihood ◽  
Number Of Patients ◽  
Practical Recommendations ◽  
Specific Expertise

Congenital heart defects (CHD) are the most common congenital defects. As a substantial number of patients with CHD now reach the reproductive age, the cardiologist dealing with grown up patients with CHD is confronted with questions of patients regarding impact of their CHD on pregnancy and offspring, and genetic counselling is becoming more relevant to clinical practice. Developments in the field of clinical genetics do not always facilitate the clinicians' knowledge and reasoning. Interpretation of the often-large DNA datasets is challenging, especially in the light of phenotypic heterogeneity and incomplete penetrance, and requires specific expertise. In this chapter the genetics of CHD are addressed. An overview of 'causative' genes is provided, i.e. genes with a high likelihood to be involved in the development of human CHD and found so far to harbour (likely) pathogenic mutations in patients. In addition, the challenges and limitations in determining such genes are addressed and pitfalls in interpreting DNA variants in these genes discussed. The fact that single genes may in some instances be associated with different forms of CHD, may be explained by the broad range of cellular contribution during embryology, which will be briefly addressed. Finally, practical recommendations in addressing the genetics of CHD are provided.

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