Faculty Opinions recommendation of De novo mutations in histone-modifying genes in congenital heart disease.

2017 ◽  
Author(s):  
David Brook
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
De Novo ◽  
De Novo Mutations ◽  
Modifying Genes

scholarly journals De novo mutations in histone-modifying genes in congenital heart disease

Nature ◽  
2013 ◽  
Vol 498 (7453) ◽  
pp. 220-223 ◽  
Author(s):  
Samir Zaidi ◽  
Murim Choi ◽  
Hiroko Wakimoto ◽  
Lijiang Ma ◽  
Jianming Jiang ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
De Novo ◽  
De Novo Mutations ◽  
Modifying Genes

scholarly journals Molecular Genetics and Complex Inheritance of Congenital Heart Disease

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1020
Author(s):  
Nicholas S. Diab ◽  
Syndi Barish ◽  
Weilai Dong ◽  
Shujuan Zhao ◽  
Garrett Allington ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Throughput ◽  
Congenital Heart ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Copy Number Variations ◽  
De Novo Mutations ◽  
Genomic Technologies ◽  
Chd Risk

Congenital heart disease (CHD) is the most common congenital malformation and the leading cause of mortality therein. Genetic etiologies contribute to an estimated 90% of CHD cases, but so far, a molecular diagnosis remains unsolved in up to 55% of patients. Copy number variations and aneuploidy account for ~23% of cases overall, and high-throughput genomic technologies have revealed additional types of genetic variation in CHD. The first CHD risk genotypes identified through high-throughput sequencing were de novo mutations, many of which occur in chromatin modifying genes. Murine models of cardiogenesis further support the damaging nature of chromatin modifying CHD mutations. Transmitted mutations have also been identified through sequencing of population scale CHD cohorts, and many transmitted mutations are enriched in cilia genes and Notch or VEGF pathway genes. While we have come a long way in identifying the causes of CHD, more work is required to end the diagnostic odyssey for all CHD families. Complex genetic explanations of CHD are emerging but will require increasingly sophisticated analysis strategies applied to very large CHD cohorts before they can come to fruition in providing molecular diagnoses to genetically unsolved patients. In this review, we discuss the genetic architecture of CHD and biological pathways involved in its pathogenesis.

scholarly journals De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies

Science ◽  
2015 ◽  
Vol 350 (6265) ◽  
pp. 1262-1266 ◽  
Author(s):  
J. Homsy ◽  
S. Zaidi ◽  
Y. Shen ◽  
J. S. Ware ◽  
K. E. Samocha ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Anomalies ◽  
Congenital Heart ◽  
De Novo ◽  
De Novo Mutations

scholarly journals De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
W. Scott Watkins ◽  
E. Javier Hernandez ◽  
Sergiusz Wesolowski ◽  
Brent W. Bisgrove ◽  
Ryan T. Sunderland ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Architecture ◽  
Congenital Heart ◽  
De Novo ◽  
Disease Genes ◽  
Compound Heterozygous ◽  
Modifying Genes ◽  
Whole Exome ◽  
Background Mutation Rate

Abstract The genetic architecture of sporadic congenital heart disease (CHD) is characterized by enrichment in damaging de novo variants in chromatin-modifying genes. To test the hypothesis that gene pathways contributing to de novo forms of CHD are distinct from those for recessive forms, we analyze 2391 whole-exome trios from the Pediatric Cardiac Genomics Consortium. We deploy a permutation-based gene-burden analysis to identify damaging recessive and compound heterozygous genotypes and disease genes, controlling for confounding effects, such as background mutation rate and ancestry. Cilia-related genes are significantly enriched for damaging rare recessive genotypes, but comparatively depleted for de novo variants. The opposite trend is observed for chromatin-modifying genes. Other cardiac developmental gene classes have less stratification by mode of inheritance than cilia and chromatin-modifying gene classes. Our analyses reveal dominant and recessive CHD are associated with distinct gene functions, with cilia-related genes providing a reservoir of rare segregating variation leading to 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

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.

scholarly journals FISH spots microdeletion in heart defects

2009 ◽  
Vol 15 (S3) ◽  
pp. 5-6
Author(s):  
P. Ferraz-Gameiro ◽  
J. Ferrão ◽  
C. Mendes ◽  
L. M. Pires ◽  
E. Matoso ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
De Novo ◽  
Heart Defects ◽  
Autosomal Dominant Trait ◽  
Conotruncal Malformations ◽  
Wide Range ◽  
22Q11.2 Microdeletion ◽  
Made In

AbstractThe 22q11.2 microdeletion is found in most of DiGeorge and velocardiofacial syndromes. These individuals have a wide range of anomalies including congenital heart disease, palatal abnormalities, characteristic facial features, hypocalcaemia, immune deficiency, and learning difficulties. Congenital heart disease, particularly conotruncal malformations are associated with 29% of deletions. This syndrome may be inherited as an autosomal dominant trait, but the majority of patients (93%) have a de novo deletion. To access the presence of the microdeletion in those individuals whose phenotipic changes suggested abnormalities in chromosome 22, a study has been made in several children with congenital heart defects.

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