Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Genetics of Congenital Heart Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01192048
Recruitment Status : Recruiting
First Posted : August 31, 2010
Last Update Posted : August 24, 2021
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Vidu Garg, Nationwide Children's Hospital

Brief Summary:
Congenital heart disease (CHD) is the most common type of birth defect but the cause for the majority of cardiac birth defects remains unknown. Numerous epidemiologic studies have demonstrated evidence that genetic factors likely play a contributory, if not causative, role in CHD. While numerous genes have been identified by us and other investigators using traditional genetic approaches, but these genes only account for a minority of the non-syndromic CHDs. Therefore, we are now utilizing whole exome sequencing (WES), with the addition of more traditional genetic techniques such as chromosomal microarray or traditional linkage analysis, to identify genetic causes of familial and isolated CHD. With WES we are able to sequence all of the genes of an individual and apply different data analysis techniques based on whether we are analyzing a multiplex family or a cohort of trios (mother, father and child with CHD) with a specific isolated CHD. Therefore, WES is a robust method for identification of novel genetic causes of CHD which will have important diagnostic and therapeutic consequences for these children.

Condition or disease Intervention/treatment
Congenital Heart Disease Other: Blood Sample Collection

Detailed Description:

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 (Garg, 2006). 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). 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 (Srivastava and Olson, 2000). Although this approach has been successful (Schluterman, 2007; Rajagopal, 2007; Tomita-Mitchell, 2007; Richards, 2008; Ransom, 2009), it is also limited to the candidate gene lists.

Whole exome sequencing (WES) is a recently developed massively multiplexed sequencing technology that allows for the sequencing of all of the expressed genes. Therefore, this method can be applied to multiplex families and cohorts of sporadic cases to identify genetic causes of CHD in an unbiased manner. WES is dependent on the technical and bioinformatics prowess of the personnel running the WES 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). As other groups have successfully implemented WES into their CHD gene discovery toolkit (Zaidi, 2013; El Turki, 2014)), we expect to do the same. WES is powerful genetic tool that can be used in isolation or in conjunction with other types of genetic analysis (i.e. array comparative genomic hybridization, single nucleotide polymorphisms (SNP) arrays, traditional linkage analysis) to increase the yield of these investigations.

Layout table for study information
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

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
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.
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 sequencing.

Primary Outcome Measures :
  1. 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
Blood samples will be collected in vacuum tubes containing acid citrate dextrose (ACD). Lymphocytes from blood drawn in appropriate anticoagulant (ACD) may be stored for subsequent immortalization. DNA will be extracted from these samples for analysis.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
cardiology clinic sample, community 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01192048

Layout table for location contacts
Contact: Katherine J Myers, MS, CGC 614-355-6388

Layout table for location information
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Principal Investigator: Vidu Garg, MD         
Sponsors and Collaborators
Nationwide Children's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Layout table for investigator information
Principal Investigator: Vidu Garg, MD The Research Institute at Nationwide Children's Hospital
Publications of Results:

Other Publications:
Layout table for additonal information
Responsible Party: Vidu Garg, Director and Professor, Nationwide Children's Hospital 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: August 24, 2021
Last Verified: August 2021
Keywords provided by Vidu Garg, Nationwide Children's Hospital:
Congenital Heart Disease
birth defect
direct sequencing
single nucleotide polymorphism
whole genome array comparative genomic hybridization
chromosomal copy number change
nucleotide sequence variation
exome sequencing
whole exome sequencing
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities