scholarly journals Genetic Testing Protocol Reduces Costs and Increases Rate of Genetic Diagnosis in Infants with Congenital Heart Disease

2017 ◽  
Vol 38 (7) ◽  
pp. 1465-1470 ◽  
Author(s):  
Gabrielle C. Geddes ◽  
Donald Basel ◽  
Peter Frommelt ◽  
Aaron Kinney ◽  
Michael Earing
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Testing ◽  
Congenital Heart ◽  
Genetic Diagnosis ◽  
Testing Protocol

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.

The Diagnostic Yield of Prenatal Genetic Technologies in Congenital Heart Disease: A Prospective Cohort Study

2021 ◽  
pp. 1-8
Author(s):  
Fionnuala Mone ◽  
Bethany K. Stott ◽  
Susan Hamilton ◽  
Anna N. Seale ◽  
Elizabeth Quinlan-Jones ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Cohort Study ◽  
Heart Disease ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Congenital Heart ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
Uncertain Significance ◽  
Conotruncal Anomalies

<b><i>Introduction:</i></b> The objective was to evaluate: (i) the proportion of prenatally diagnosed congenital heart disease (CHD) associated with an abnormal quantitative fluorescence-PCR (QF-PCR), chromosome microarray (CMA), and exome sequencing (ES) result; and (ii) the diagnostic yield of these technologies based on CHD category and presence of extra-cardiac anomalies (ECAs). <b><i>Methods:</i></b> This prospective cohort study was set across 12 UK foetal medicine centres. All cases underwent QF-PCR, CMA, and ES, and the diagnostic yield in <i>n</i> = 147 cases of prenatally diagnosed CHD was assessed. <b><i>Results:</i></b> In 34.7% (<i>n</i> = 51/147), a genetic diagnosis was obtained. Using a stepwise testing strategy, the diagnostic yield for QF-PCR, CMA, and ES was 15.6% (<i>n</i> = 23/147), 13.7% (<i>n</i> = 17/124), and 10.2% (<i>n</i> = 11/107), respectively. Abnormal QF-PCR/shunt (septal) defects 31.4% (<i>n</i> = 11/35), <i>p</i> = 0.046, and abnormal CMA/conotruncal anomalies 22.7% (<i>n</i> = 10/44), <i>p</i> = 0.04, had significant associations. Monogenic variants were commonest in complex CHD 36.4% (<i>n</i> = 4/11). Multisystem CHD had a greater diagnostic yield overall compared to isolated OR 2.41 (95% CI, 1.1–5.1), particularly in association with brain and gastrointestinal tract anomalies. The proportion of variants of uncertain significance was 4.7% (<i>n</i> = 5/107) with ES, with none in the CMA group. <b><i>Conclusion:</i></b> In the era of prenatal ES, there remains an important role for QF-PCR and CMA. Identification of monogenic pathologic variants further allows delineation of prognosis in CHD.

scholarly journals Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants

2019 ◽  
Vol 29 (4) ◽  
pp. 566-579 ◽  
Author(s):  
Gavin Chapman ◽  
Julie L M Moreau ◽  
Eddie I P ◽  
Justin O Szot ◽  
Kavitha R Iyer ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Cultured Cells ◽  
Heart Defects ◽  
Genetic Diagnosis ◽  
Notch Pathway ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract Congenital heart disease (CHD) is the most common birth defect and brings with it significant mortality and morbidity. The application of exome and genome sequencing has greatly improved the rate of genetic diagnosis for CHD but the cause in the majority of cases remains uncertain. It is clear that genetics, as well as environmental influences, play roles in the aetiology of CHD. Here we address both these aspects of causation with respect to the Notch signalling pathway. In our CHD cohort, variants in core Notch pathway genes account for 20% of those that cause disease, a rate that did not increase with the inclusion of genes of the broader Notch pathway and its regulators. This is reinforced by case-control burden analysis where variants in Notch pathway genes are enriched in CHD patients. This enrichment is due to variation in NOTCH1. Functional analysis of some novel missense NOTCH1 and DLL4 variants in cultured cells demonstrate reduced signalling activity, allowing variant reclassification. Although loss-of-function variants in DLL4 are known to cause Adams-Oliver syndrome, this is the first report of a hypomorphic DLL4 allele as a cause of isolated CHD. Finally, we demonstrate a gene-environment interaction in mouse embryos between Notch1 heterozygosity and low oxygen- or anti-arrhythmic drug-induced gestational hypoxia, resulting in an increased incidence of heart defects. This implies that exposure to environmental insults such as hypoxia could explain variable expressivity and penetrance of observed CHD in families carrying Notch pathway variants.

scholarly journals UTILITY OF GENETIC TESTING IN INFANTS WITH ISOLATED CONGENITAL HEART DISEASE

2017 ◽  
Vol 69 (11) ◽  
pp. 635
Author(s):  
Kaitlin L'Italien ◽  
Sara Fitzgerald-Butt ◽  
Janet Simsic ◽  
Kim McBride ◽  
Jessica Bowman ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Testing ◽  
Congenital Heart

Genetic Testing in Congenital Heart Disease

2013 ◽  
Vol 4 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Kimberly Y. Lin ◽  
Lisa C. A. D’Alessandro ◽  
Elizabeth Goldmuntz
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Testing ◽  
Congenital Heart

YIELD OF GENETIC TESTING IN NEONATES WITH CONGENITAL HEART DISEASE AND ASSOCIATION WITH CLINICAL OUTCOMES

2019 ◽  
Vol 73 (9) ◽  
pp. 603
Author(s):  
Shannon Nees ◽  
Katharine Press Callahan ◽  
Sonya Besagar ◽  
Teresa Lee ◽  
Volkan Okur ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Testing ◽  
Clinical Outcomes ◽  
Congenital Heart

scholarly journals Genetic counselling and testing in adults with congenital heart disease: A consensus document of the ESC Working Group of Grown-Up Congenital Heart Disease, the ESC Working Group on Aorta and Peripheral Vascular Disease and the European Society of Human Genetics

2019 ◽  
Vol 27 (13) ◽  
pp. 1423-1435 ◽  
Author(s):  
Julie De Backer ◽  
Antoine Bondue ◽  
Werner Budts ◽  
Arturo Evangelista ◽  
Pastora Gallego ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Testing ◽  
European Society ◽  
Working Group ◽  
Congenital Heart ◽  
Human Genetics ◽  
Peripheral Vascular ◽  
Consensus Document ◽  
Aortic Pathology

Thanks to a better knowledge of the genetic causes of many diseases and an improvement in genetic testing techniques, genetics has gained an important role in the multidisciplinary approach to diagnosis and management of congenital heart disease and aortic pathology. With the introduction of strategies for precision medicine, it is expected that this will only increase further in the future. Because basic knowledge of the indications, the opportunities as well as the limitations of genetic testing is essential for correct application in clinical practice, this consensus document aims to give guidance to care-providers involved in the follow-up of adults with congenital heart defects and/or with hereditary aortic disease. This paper is the result of a collaboration between the ESC Working Group of Grown-Up Congenital Heart Disease, the ESC Working Group on Aorta and Peripheral Vascular Disease and the European Society of Human Genetics. Throughout the document, the importance of correct counseling in the process of genetic testing is emphasized, indications and timing for genetic studies are discussed as well as the technical modalities of genetic testing. Finally, the most important genetic diseases in adult congenital heart disease and aortic pathology are also discussed.

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