scholarly journals Identification of Novel Single-Nucleotide Variants With Potential of Mediating Malfunction of MicroRNA in Congenital Heart Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Wangkai Liu ◽  
Liangping Cheng ◽  
Ken Chen ◽  
Jialing Wu ◽  
Rui Peng ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Target Genes ◽  
Heart Defects ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Downstream Target ◽  
Gene Dysregulation ◽  
Great Vessels

Congenital heart defects (CHDs) represent the most common human birth defects. Our previous study indicates that the malfunction of microRNAs (miRNAs) in cardiac neural crest cells (NCCs), which contribute to the development of the heart and the connected great vessels, is likely linked to the pathogenesis of human CHDs. In this study, we attempt to further search for causative single-nucleotide variants (SNVs) from CHD patients that mediate the mis-regulating of miRNAs on their downstream target genes in the pathogenesis of CHDs. As a result, a total of 2,925 3′UTR SNVs were detected from a CHD cohort. In parallel, we profiled the expression of miRNAs in cardiac NCCs and found 201 expressed miRNAs. A combined analysis with these data further identified three 3′UTR SNVs, including NFATC1 c.*654C>T, FGFRL1 c.*414C>T, and CTNNB1 c.*729_*730insT, which result in the malfunction of miRNA-mediated gene regulation. The dysregulations were further validated experimentally. Therefore, our study indicates that miRNA-mediated gene dysregulation in cardiac NCCs could be an important etiology of congenital heart disease, which could lead to a new direction of diagnostic and therapeutic investigation on congenital heart disease.

scholarly journals Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

2021 ◽  
Vol 11 (6) ◽  
pp. 562
Author(s):  
Olga María Diz ◽  
Rocio Toro ◽  
Sergi Cesar ◽  
Olga Gomez ◽  
Georgia Sarquella-Brugada ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart Defects ◽  
Congenital Malformations ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Genetic Diagnosis ◽  
Single Nucleotide Variants ◽  
Personalized Approach

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

CONGESTIVE HEART FAILURE

PEDIATRICS ◽  
1956 ◽  
Vol 18 (3) ◽  
pp. 491-500 ◽  
Author(s):  
John D. Keith
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Heart Muscle ◽  
Congenital Heart ◽  
Heart Defects ◽  
Age At Onset ◽  
Pericardial Disease ◽  
Great Vessels

HEART failure is associated with an inability of the heart to empty itself adequately, with the result that there is a high venous filling pressure and a decrease in the effective work done by the heart muscle. There are several factors that, if sufficiently severe, will produce congestive heart failure in either infancy or childhood. These include valvular obstruction or insufficiency; mechanical obstruction of the heart as a whole, as in pericardial disease; the physical effects of large intracardiac shunts which increase the load on one or both ventricles; the presence of raised pressure in the pulmonary or systemic circulation; inflammatory reactions in the heart muscle or oxygen lack; and, finally, certain metabolic disturbances, such as hyperthyroidism or hypothyroidism. One or more of these factors may be operating in the same child, as in rheumatic fever where myocarditis is associated with valvular insufficiency, or in congenital heart disease with pulmonary stenosis and patent foramen ovale, where the right ventricle has a high pressure to maintain and is at the same time being offered cyanotic blood from the coronaries. PATIENT MATERIAL In analyzing 1,580 cases of congenital heart disease at the Hospital for Sick Children, Toronto, 20 per cent were found to have had failure at some time. In 90 per cent of these failure occurred in the first year of life. A list of the various causes of heart failure in the pediatric age group in order of frequency follows. [see table in source pdf] In certain types of heart defects failure develops in characteristic age groups. For example, during the first week of life the most common cause of heart failure is aortic atresia. From 1 week to 1 month, coarctation of the aorta leads. From 1 to 2 months, transposition of the great vessels predominates. From 2 to 3 months, endocardial fibroelastosis is the chief cause of heart failure, with transportation of the great vessels second to it. The actual incidence of type of heart defect in relation to age at onset of heart failure is as follows.

scholarly journals Identification and analysis of KLF13 variants in patients with congenital heart disease

2019 ◽  
Author(s):  
Wenjuan Li ◽  
Baolei Li ◽  
Tingting Li ◽  
Ergeng Zhang ◽  
Qingjie Wang ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Transcription Factor ◽  
Heart Disease ◽  
Subcellular Localization ◽  
Protein Expression ◽  
Heart Development ◽  
Congenital Heart ◽  
Target Genes ◽  
Healthy Controls ◽  
Downstream Target

Abstract Background: The protein Kruppel-like factor 13 (KLF13) is a member of the KLF family that has been identified as a novel cardiac transcription factor which is involved in heart development. However, the relationship between KLF13 variants and CHDs in humans remains largely unknown. The present study aimed to screen the KLF13 variants in CHDs patients and genetically analyze the function of these variants. Methods: KLF13 variants were sequenced in a cohort of 309 CHD patients and population-matched healthy controls (n = 200) using targeted sequencing. To investigate the effect of variants on the functional ability of the KLF13 protein, the expressions and subcellular localization of protein, as well as the transcriptional activities of downstream genes and physically interacted with other transcription factor were assessed. Results: Two novel heterozygous variants, c.487C>T (P163S) and c.467G>A (S156N), were identified in two out of 309 CHDs patients with Tricuspid-valve atresia and transposition of the great arteries, respectively. No variants were found among healthy controls. The variant c.467G>A (S156N) increased protein expression and enhanced functionality compared with that of wild-type, without affecting the subcellular localization. The other variant, c.487C>T (P163S), did not show any abnormalities in protein expression and subcellular localization, however it eliminated the transcriptional activities of downstream target genes and physically interacted with TBX5, another cardiac transcription factor. Conclusion: Our results show that the S156N and P163S variants contributed to CHD etiology. Additionally, our findings suggest that KLF13 may be a potential gene contributing to congenital heart disease.

scholarly journals Early Prenatal Diagnosis of an Extremely Rare Association of Down Syndrome and Transposition of the Great Vessels

2019 ◽  
Vol 70 (7) ◽  
pp. 2574-2578
Author(s):  
Cristina Crenguta Albu ◽  
Dinu-Florin Albu ◽  
Stefan-Dimitrie Albu ◽  
Anca Patrascu ◽  
Ana-Roxana Musat ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Down Syndrome ◽  
Heart Disease ◽  
Prenatal Diagnosis ◽  
Trisomy 21 ◽  
Congenital Heart ◽  
Heart Defects ◽  
Live Births ◽  
Cardiac Malformations ◽  
Great Vessels

Every year, an estimated 7.9 million infants (6% of worldwide births) are born with serious�birth defects [1].�Congenital cardiovascular defects make up one of the largest groups of severe congenital malformations [2].The incidence of congenital heart defects in different studies varies from about 4/1,000 to 50/1,000 live births [3].� Congenital heart disease is frequently described in patients with Down syndrome and is the main cause of death in this population during the first two years of life [4].�Trisomy 21 with cardiovascular malformations have a maternal age-adjusted regional prevalence of 4.33/10,000 for the white population and 3.70/10,000 for the nonwhite population [5].�Prenatal diagnosis of�congenital�heart disease is important for proper perinatal and neonatal management, as congenital cardiac malformations occurs in approximately eight of 1000 live births [6]. We present an extremely rare case of early prenatal diagnosis and management of a fetus with trisomy 21 associated with the transposition of the great vessels, one of the most mysterious congenital cardiac malformations.

scholarly journals THE ROLE OF GENETICS IN THE UNDERSTANDING OF COMPLEX CONGENITAL HEART DISEASES

2022 ◽  
Vol 54 (4) ◽  
pp. 383-384
Author(s):  
Sana Ashiq ◽  
Muhammad Farooq Sabar
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Generation Sequencing

One of the most dynamic organs in the human body is the heart. Cardiac development is regulated by two key factors including signaling and transcriptional pathways. Thus, during the development of the fetus, any factor that disrupts the normal functioning of these factors may lead toward congenital heart defects (CHDs). Congenital heart disease is a complex multifactorial disease that involves both environmental and genetic factors.1,2 It is defined as any defect that occurs during heart development either in the cardiac structure or its associated vessels.3 Globally, it is one of the most common reasons for infant mortality and one of the most common birth defects in paediatric patients. As a rough estimate, 8 infants in every thousand live births are born with this fatal disease.4 Every year, in Pakistan approximately 40,000 children suffered from CHDs.5 Clinically depending upon the disease severity congenital heart diseases can be divided into two major subgroups one is non-syndromic and the other is syndromic. And among all these defects cardiac septation defects are the most common accounting for approximately 50% of the cases.6 It can be further sub-grouped as isolated lesions or complex diseases in combination with other heart defects.3  The exact mechanism involved in the pathogenesis of the congenital heart remains poorly understood but the most probable mechanism is multifactorial. Recent investigations suggest the role of epigenetic factors, micro RNA and small non-coding RNAs in the development of congenital heart defects. Moreover, advancements in molecular techniques including next-generation sequencing (NGS) helps in further detecting the genetic causes of CHDs such as the novel single nucleotide polymorphisms (SNPs) and copy number variants (CNVs).7 The current approaches used for genetic diagnosis of paediatric patients suffering from CHDs include karyotype analysis, copy number variation analysis, next-generation sequencing, and whole-genome or whole-exome sequencing. The targeted NGS relies on the selected region of know gene of interest and compared to whole genome or exome sequencing it provides us deeper gene coverage with easy variant detection at a lower cost. It provides robust detection of deletions, insertion and single nucleotide polymorphisms which chromosomal microarray analysis (CMA) and karyotyping cannot detect. To date, many pathogenic variants in different genes such as CITED2, CHD7, ZFPM2, MYH6 and KMT2D have been investigated by using targeted NGS. While whole-exome or genome sequencing help in the discovery of genes involves in the pathogenesis of congenital heart defects as it gives us more resolution at a single base-pair level. Thus accurate genetic diagnosis can be done by using the appropriate diagnostic techniques that can ultimately help in better patient counseling and clinical outcome.8 Furthermore, personalized medicines or finding mutations responsible for individual congenital heart disease patients can direct to better outcomes and approaches for each cardiac malformation phenotype. Thus, ultimately combined data of patients genotypic and phenotypic following well-designed guidelines will accelerate the translation of each SNP information into better treatment and clinical insights.9 Keywords: NGS, Single nucleotide polymorphisms, CHDs. References Ashiq S, Ashiq K. Genetic perspective of the congenital heart disease. Pak Heart J. 2020;53(3):1-3. Wang H, Liu Y, Li Y, Wang W, Li L, Meng M, et al. Analysis of NKX2-5 in 439 Chinese patients with sporadic atrial septal defect. Medical Sci Monit. 2019;25:2756. Ashiq S, Ashiq K, Sabar MF. The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis. Egypt Heart J. 2021;73(1):1-9. Zhao M, Diao J, Huang P, Li J, Li Y, Yang Y, et al. Association of maternal diabetes mellitus and polymorphisms of the NKX2. 5 gene in children with congenital heart disease: a single centre-based case-control study. J Diabetes Res. 2020;2020:3854630. Hussain S, Sabir MU, Afzal M, Asghar I. Incidence of congenital heart disease among neonates in a neonatal unit of a tertiary care hospital. J Pak Med Assoc. 2014;64(2):175-8. Wolf M, Basson CT. The molecular genetics of congenital heart disease: a review of recent developments. Curr Opin Cardiol. 2010;25(3):192. Muntean I, Togănel R, Benedek T. Genetics of congenital heart disease: past and present. Biochem Genet. 2017;55(2):105-23. Qiao F, Hu P, Xu Z. Application of next-generation sequencing for the diagnosis of fetuses with congenital heart defects. Curr Opin Obstet Gynecol. 2019;31(2):132-8. Pasipoularides A. The new era of whole-exome sequencing in congenital heart disease: brand-new insights into rare pathogenic variants. J Thorac Dis. 2018;10(Suppl 17):S1923-29.

The Impact of Congenital Heart Disease on Cognitive and Behavioral Functioning

2010 ◽  
Author(s):  
Jo Wray
Keyword(s):  
Congenital Heart Disease ◽  
Blood Flow ◽  
Heart Disease ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Congenital Abnormalities ◽  
Heart Defects ◽  
Survival Rates ◽  
Arterial Circulation ◽  
Great Vessels

Congenital heart disease (CHD) has been defined as “. . . a gross structural abnormality of the heart or intrathoracic great vessels that is actually or potentially of functional significance” (Mitchell, Korones, and Berendes 1971). Congenital heart disease is the most common single group of congenital abnormalities, accounting for about 30% of the total. The incidence is reported as varying between 0.3% and 1% of all live births. Ten to 15% of children with congenital heart defects have more than one cardiac abnormality; up to one-third also have one or more associated noncardiac congenital abnormalities (Wernovsky 2006). Although some forms of CHD are minor and do not require any medical or surgical intervention, others are very complex and may necessitate a series of staged surgical procedures and/or require life-long medications. Significant improvements in medical and surgical techniques have resulted in increasing numbers of children and adults living with CHD, and it is currently anticipated that 80%–85% of children born with CHD today will survive into adulthood (British Cardiac Society 2002). However, although survival rates have improved dramatically over the last 40 years or so, morbidity remains a concern. Congenital heart defects can be broadly subdivided into two groups, based on changes in the circulation. Acyanotic defects may be due to either a left-to-right shunt or to an obstructive lesion; there is no mixing of desaturated blood in the systemic arterial circulation. With cyanotic defects, there may be either increased or diminished pulmonary flow, and desaturated blood enters the systemic arterial circulation, regardless of whether cyanosis is clinically evident. Unsaturated venous blood bypassing the lungs can result in secondary polycythemia, which is a compensatory mechanism to carry more oxygen to the tissues. This causes increased viscosity, which in turn results in sluggish blood circulation and impeded blood flow, particularly in the capillaries. Poor peripheral blood flow and clubbing of the fingers and toes can result, breathlessness and fatigue often result in a reduced exercise tolerance, and growth may be affected.

scholarly journals Down syndrome and congenital heart disease: perioperative planning and management

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Dennis R. Delany ◽  
Stephanie S. Gaydos ◽  
Deborah A. Romeo ◽  
Heather T. Henderson ◽  
Kristi L. Fogg ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Down Syndrome ◽  
Cardiac Surgery ◽  
Heart Disease ◽  
Congenital Heart ◽  
Single Ventricle ◽  
Heart Defects ◽  
Careful Consideration ◽  
Children With Down Syndrome ◽  
Perioperative Planning

AbstractApproximately 50% of newborns with Down syndrome have congenital heart disease. Non-cardiac comorbidities may also be present. Many of the principles and strategies of perioperative evaluation and management for patients with congenital heart disease apply to those with Down syndrome. Nevertheless, careful planning for cardiac surgery is required, evaluating for both cardiac and noncardiac disease, with careful consideration of the risk for pulmonary hypertension. In this manuscript, for children with Down syndrome and hemodynamically significant congenital heart disease, we will summarize the epidemiology of heart defects that warrant intervention. We will review perioperative planning for this unique population, including anesthetic considerations, common postoperative issues, nutritional strategies, and discharge planning. Special considerations for single ventricle palliation and heart transplantation evaluation will also be discussed. Overall, the risk of mortality with cardiac surgery in pediatric patients with Down syndrome is no more than the general population, except for those with functional single ventricle heart defects. Underlying comorbidities may contribute to postoperative complications and increased length of stay. A strong understanding of cardiac and non-cardiac considerations in children with Down syndrome will help clinicians optimize perioperative care and long-term outcomes.

scholarly journals Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

2014 ◽  
Vol 32 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Felipe Alves Mourato ◽  
Lúcia Roberta R. Villachan ◽  
Sandra da Silva Mattos
Keyword(s):  
Congenital Heart Disease ◽  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Heart Disease ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Diseases ◽  
Heart Defects ◽  
Descriptive Analysis ◽  
Atrioventricular Septal Defect

OBJECTIVE:To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis.METHODS:Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7.RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age.CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension.

HEMANGIOMA OF THE LIVER WITH HEART FAILURE: A CASE REPORT

PEDIATRICS ◽  
1954 ◽  
Vol 14 (2) ◽  
pp. 117-121
Author(s):  
ROBERT W. WINTERS ◽  
SAUL J. ROBINSON ◽  
GEORGE BATES
Keyword(s):  
Heart Failure ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Case Report ◽  
Cardiac Hypertrophy ◽  
Cardiac Failure ◽  
Congenital Heart ◽  
Signs And Symptoms ◽  
Post Mortem ◽  
Great Vessels

A case of multiple hemangiomata of the liver is reported in an infant who presented signs and symptoms strongly suggesting congenital heart disease. The post mortem examination revealed no gross anomalies of the heart or great vessels, but did show a heart with cardiac hypertrophy. A mechanism to explain the cardiac failure in this case is discussed.

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