Genetics of Congenital Heart Disease
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ClinicalTrials.gov Identifier: NCT01192048 |
Recruitment Status :
Recruiting
First Posted : August 31, 2010
Last Update Posted : September 28, 2023
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Condition or disease | Intervention/treatment |
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Congenital Heart Disease | Other: Blood Sample Collection |
Congenital heart disease (CHD) is the most common type of birth defect, but the etiology of CHD remains largely unknown. Genetic causes have been discovered for both syndromic and non-syndromic CHD utilizing several genetic approaches (Yasuhara and Garg, 2021). The majority of these genetic causes have found by studying large families with autosomal dominant congenital heart disease and my laboratory has successfully used this methodology in the past (Garg, 2003; Garg 2005; Pan, 2009; Bennett, 2022). Although these positional cloning approaches are very powerful, they are limited by rare nature of multi-generation pedigrees and are limited to milder forms of CHD that have allowed for the generation of large kindreds.
The other method that has traditionally been utilized to identify genetic causes of CHD is the screening of large populations of children with sporadic (non-familial) cases of CHD for genetic abnormalities (nucleotide sequence variations in candidate genes for CHD or for chromosomal copy number changes that involve CHD-candidate genes). This work has been tedious as a large number of candidate genes have been implicated as potentially responsible for CHD in humans (Choudhury and Garg, 2022). Although this approach has been successful (Schluterman, 2007; Maitra, 2010; Chang, 2013; Bonachea, 2014), it is also limited to the candidate gene lists.
Whole exome sequencing (WES) is a next-generation sequencing technology that allows for the sequencing of all of the expressed genes. Our group, in addition to several others (LaHaye, 2016; Gordon, 2022), has been utilizing WES technology for CHD gene discovery. Our group has progressed to utilizing whole genome sequencing (WGS), a next-generation sequencing technology that allows for the sequencing of all genetic material (including genomic regions that are not sequenced in WES), in our analysis for CHD gene discovery. Therefore, these sequencing methods can be applied to multiplex families and cohorts of sporadic cases to identify genetic causes of CHD in an unbiased manner. Genomic sequencing is dependent on the technical and bioinformatics prowess of the personnel running the sequencing and the controlling the data pipeline. The Institute of Genomic Medicine at Nationwide Children's Hospital (NCH) is both technically skilled and have developed their own powerful data pipeline (Kelly, 2015). WGS is a powerful genetic tool that can be used in isolation or in conjunction with other types of genetic analysis to increase the yield of these investigations.
Study Type : | Observational |
Estimated Enrollment : | 1000 participants |
Observational Model: | Family-Based |
Time Perspective: | Prospective |
Official Title: | Genetics Testing of Individuals and Families With Congenital Heart Disease |
Study Start Date : | December 2009 |
Estimated Primary Completion Date : | December 2025 |
Estimated Study Completion Date : | December 2025 |
Group/Cohort | Intervention/treatment |
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Study Subjects
Individuals with Congenital Heart Disease and family members with or without Congenital Heart Disease. A blood sample collection will be required for all study participants.
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Other: Blood Sample Collection
Blood sample collection for direct sequencing, microarray, single nucleotide polymorphism, whole-genome array comparative genomic hybridization DNA analyses, and/or whole exome or genome sequencing. |
- Identification of novel genetic contributors to congenital heart defects [ Time Frame: up to 3 years, from date of genetic analysis to completion of genetic data analysis or identification of novel genetic contributors, whichever comes first ]Novel genetic abnormalities that are found to be associated with congenital heart defects in humans
Biospecimen Retention: Samples With DNA
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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Subjects must have a diagnosis of Congenital Heart Disease or be related to individuals with Congenital Heart Disease.
Exclusion Criteria:
- Healthy individuals unrelated to those with Congenital Heart Disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01192048
Contact: Katherine M Spayde, MS, CGC | 614-355-6388 | katherine.spayde@nationwidechildrens.org |
United States, Ohio | |
Nationwide Children's Hospital | Recruiting |
Columbus, Ohio, United States, 43205 | |
Principal Investigator: Vidu Garg, MD |
Principal Investigator: | Vidu Garg, MD | The Research Institute at Nationwide Children's Hospital |
Other Publications:
Responsible Party: | Vidu Garg, Director and Professor, Nationwide Children's Hospital |
ClinicalTrials.gov Identifier: | NCT01192048 |
Other Study ID Numbers: |
IRB09-00339 R01HL109758-03 ( U.S. NIH Grant/Contract ) |
First Posted: | August 31, 2010 Key Record Dates |
Last Update Posted: | September 28, 2023 |
Last Verified: | September 2023 |
Congenital Heart Disease birth defect genetics gene DNA direct sequencing microarray |
single nucleotide polymorphism whole genome array comparative genomic hybridization chromosomal copy number change nucleotide sequence variation exome sequencing whole exome sequencing whole genome sequencing |
Heart Diseases Heart Defects, Congenital Cardiovascular Diseases Cardiovascular Abnormalities Congenital Abnormalities |