scholarly journals A Multi-Omics Approach Using a Mouse Model of Cardiac Malformations for Prioritization of Human Congenital Heart Disease Contributing Genes

2021 ◽  
Vol 8 ◽  
Author(s):  
Adrianna Matos-Nieves ◽  
Sathiyanarayanan Manivannan ◽  
Uddalak Majumdar ◽  
Kim L. McBride ◽  
Peter White ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Mouse Model ◽  
Congenital Heart ◽  
De Novo ◽  
Transcriptional Profiling ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Cardiac Malformations ◽  
Novel Approach

Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all live births. Malformations of the cardiac outflow tract (OFT) account for ~30% of all CHD and include a range of CHDs from bicuspid aortic valve (BAV) to tetralogy of Fallot (TOF). We hypothesized that transcriptomic profiling of a mouse model of CHD would highlight disease-contributing genes implicated in congenital cardiac malformations in humans. To test this hypothesis, we utilized global transcriptional profiling differences from a mouse model of OFT malformations to prioritize damaging, de novo variants identified from exome sequencing datasets from published cohorts of CHD patients. Notch1+/−; Nos3−/− mice display a spectrum of cardiac OFT malformations ranging from BAV, semilunar valve (SLV) stenosis to TOF. Global transcriptional profiling of the E13.5 Notch1+/−; Nos3−/− mutant mouse OFTs and wildtype controls was performed by RNA sequencing (RNA-Seq). Analysis of the RNA-Seq dataset demonstrated genes belonging to the Hif1α, Tgf-β, Hippo, and Wnt signaling pathways were differentially expressed in the mutant OFT. Mouse to human comparative analysis was then performed to determine if patients with TOF and SLV stenosis display an increased burden of damaging, genetic variants in gene homologs that were dysregulated in Notch1+/−; Nos3−/− OFT. We found an enrichment of de novo variants in the TOF population among the 1,352 significantly differentially expressed genes in Notch1+/−; Nos3−/− mouse OFT but not the SLV population. This association was not significant when comparing only highly expressed genes in the murine OFT to de novo variants in the TOF population. These results suggest that transcriptomic datasets generated from the appropriate temporal, anatomic and cellular tissues from murine models of CHD may provide a novel approach for the prioritization of disease-contributing genes in patients with CHD.

scholarly journals Case report: adult onset diabetes with partial pancreatic agenesis and congenital heart disease due to a de novo GATA6 mutation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Begona Sanchez-Lechuga ◽  
Muhammad Saqlain ◽  
Nicholas Ng ◽  
Kevin Colclough ◽  
Conor Woods ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Case Report ◽  
Congenital Heart ◽  
De Novo ◽  
Adult Onset ◽  
Onset Diabetes ◽  
Adult Onset Diabetes ◽  
Pancreatic Agenesis

Endocrinal complications associated with the treatment of patients with congenital cardiac disease: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease

2008 ◽  
Vol 18 (S2) ◽  
pp. 256-264 ◽  
Author(s):  
Heather Dickerson ◽  
David S. Cooper ◽  
Paul A. Checchia ◽  
David P. Nelson
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Cardiac Disease ◽  
Congenital Heart ◽  
Healthcare Intervention ◽  
Time Interval ◽  
Quality Reporting ◽  
Cardiac Malformations ◽  
Comprehensive List ◽  
Congenital Cardiac Disease

AbstractA complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval.The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrinal systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to the endocrine system. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases.As surgical survival in children with congenital cardiac disease has improved in recent years, focus has necessarily shifted to reducing the morbidity of congenital cardiac malformations and their treatment. A comprehensive list of endocrinal complications is presented. This list is a component of a systems-based compendium of complications that will standardize terminology and thereby allow the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease will be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.

scholarly journals Penetrance of Congenital Heart Disease in a Mouse Model of Down Syndrome Depends on a Trisomic Potentiator of a Disomic Modifier

Genetics ◽  
2016 ◽  
Vol 203 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Huiqing Li ◽  
Sarah Edie ◽  
Donna Klinedinst ◽  
Jun Seop Jeong ◽  
Seth Blackshaw ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Down Syndrome ◽  
Heart Disease ◽  
Mouse Model ◽  
Congenital Heart

scholarly journals Where the congenital heart disease meets the pulmonary arterial hypertension, FLNA matters: a case report and literature review

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoxian Deng ◽  
Shanshan Li ◽  
Qiu Qiu ◽  
Bowen Jin ◽  
Menghuan Yan ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Pediatric Patients ◽  
De Novo ◽  
Wide Spectrum ◽  
Heart Defects ◽  
Pulmonary Arterial

Abstract Background Pediatric patients with genetic disorders have a higher incidence of pulmonary arterial hypertension (PAH) regardless of their heart defects. Filamin A (FLNA) mutation is recently recognized to be associated with pediatric pulmonary disorders, however, the clinical courses of PAH related to the mutation were reported in limited cases. Here, we presented a case and pooled data for better understanding of the correlation between FLNA mutation and pediatric PAH. Case presentation The patient was a 8-month-old female with repeated episodes of pneumonia. Physical examination revealed cleft lip, cleft palate and developmental retardation. Imaging examination showed a small atrial septal defect (ASD), central pulmonary artery enlargement, left upper lobe of lung atelectasis, and pulmonary infiltration. Genetic test showed she carried a de novo pathogenic variant of FLNA gene (c.5417-1G > A, p.-). Oral medications didn’t slow the progression of PAH in the patient, and she died two years later. Conclusions FLNA mutation causes rare but progressive PAH in addition to a wide spectrum of congenital heart disease and other comorbidities in pediatric patients. We highly recommend genetic testing for pediatric patients when suspected with PAH. Given the high mortality in this group, lung transplantation may offer a better outcome.

TREATMENT WITH TETRAHYDROBIOPTERIN ACCELERATES WHITE MATTER MATURATION IN A MOUSE MODEL OF PRENATAL HYPOXIA SIMULATING CONGENITAL HEART DISEASE

2018 ◽  
Vol 71 (11) ◽  
pp. A586
Author(s):  
Jennifer Romanowicz ◽  
Ludmila Korotcova ◽  
Shruti D. Ramachandra ◽  
Paul D. Morton ◽  
Amrita Cheema ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
White Matter ◽  
Mouse Model ◽  
Congenital Heart ◽  
Prenatal Hypoxia ◽  
White Matter Maturation

Regional differnces in birth prevalence of congenital heart disease in Malta

1999 ◽  
Vol 9 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Victor Grech ◽  
Hugo Agius-Muscat ◽  
Charles Savona-Ventura ◽  
Joe Pace
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Odds Ratio ◽  
Congenital Heart ◽  
The South ◽  
Birth Prevalence ◽  
North West ◽  
Live Births ◽  
Cardiac Malformations ◽  
Significant Difference

AbstractAimRecent studies have shown a correlation between environmental pollutants and increased risk of selected congenital malformations. The South-East area of the Island of Malta is much more industrialised than the more rural North-West area. The aim of this study was to test the null hypothesis that there are no regional differences in Malta in the prevalence at birth of congenital cardiac malformations. Methods: Live born infants with congenital cardiac malformations born between 1990 and 1994 were allocated to 10 areas, and thence to 2 regions of 5 areas each, so as to constitute North-West and South-East Malta. Official publications gave population totals and growth rates. Those infants with congenital cardiac malformations were then compared between the different regions using χ2and the Mann-Whitney U test.ResultsThe overall prevalence of congenital heart disease at birth was 8.8/1000 live births. The birth prevalence for the South-East region (10.1/1000 LB – 95% CI 8.4–12.3/1000 live births) was significantly higher than for the North-West (7.4/1000 live births – 95% CI 6.0–9.0/1000 live births) – p=0.03, Odds ratio 1.38 (95% CI 1.05–2.61). The Mann-Whitney U test showed a significant difference in the distribution amongst the 10 defined areas (p=0.016). The Central-East area had the highest prevalence of cardiac malformations in the entire Island – p=0.02, Odds ratio 1.70 (95% CI 1.10–2.61). Demography showed an efflux of individuals from the South-East of Malta.ConclusionThe higher prevalence of congenital heart disease noted at birth in South-East Malta is unlikely to be due to genetic factors, as these would have migrated North-West along with the population movement. An environmental factor, therefore, seems more likely to be responsible for the increased predisposition to congenital heart disease in the South-East of Malta.

Pulmonary complications associated with the treatment of patients with congenital cardiac disease: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease

2008 ◽  
Vol 18 (S2) ◽  
pp. 215-221 ◽  
Author(s):  
David S. Cooper ◽  
Jeffrey P. Jacobs ◽  
Paul J. Chai ◽  
James Jaggers ◽  
Paul Barach ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Cardiac Disease ◽  
Congenital Heart ◽  
Pulmonary Complications ◽  
Healthcare Intervention ◽  
Quality Reporting ◽  
Cardiac Malformations ◽  
Comprehensive List ◽  
Congenital Cardiac Disease

AbstractA complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval.The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrinal systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to the pulmonary system. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases.As surgical survival in children with congenital cardiac disease has improved in recent years, focus has necessarily shifted to reducing the morbidity of congenital cardiac malformations and their treatment. A comprehensive list of pulmonary complications is presented. This list is a component of a systems-based compendium of complications that will standardize terminology and thereby allow the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease will be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.

scholarly journals Micro-MRI phenotyping of a novel double-knockout mouse model of congenital heart disease

2010 ◽  
Vol 12 (Suppl 1) ◽  
pp. P1 ◽  
Author(s):  
Jon O Cleary ◽  
Karen McCue ◽  
Anthony N Price ◽  
Sarah Beddow ◽  
Roger J Ordidge ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Mouse Model ◽  
Knockout Mouse ◽  
Congenital Heart ◽  
Double Knockout ◽  
Knockout Mouse Model ◽  
Double Knockout Mouse
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