Genetics of Congenital Heart Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Nationwide Children's Hospital.
Recruitment status was  Recruiting
Information provided by (Responsible Party):
Vidu Garg, Nationwide Children's Hospital Identifier:
First received: August 30, 2010
Last updated: February 21, 2012
Last verified: February 2012

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. The investigators are researching the potential genetic causes of congenital heart disease and have taken two approaches to uncover these genetic contributors. The first requires the identification of multi-generation families with several affected members. Traditional genetic approaches can be used to analyze these families, investigators have successfully discovered several genetic causes of human CHD in this manner. This approach to identify novel genetic etiologies is limited by the scarcity of suitable pedigrees and to mild forms of congenital heart disease since severe heart defects are often lethal in childhood. The investigators are also utilizing a second approach to identify novel genetic etiologies of congenital heart disease. This approach will involve the identification of families with either isolated CHD or those with only two or three affected members. In brief, DNA (deoxyribonucleic acid) will be extracted from blood collected from individuals with CHD and/or their family members. The DNA will be analyzed by direct sequencing and/or microarray for point mutations or single nucleotide polymorphisms in known cardiac development genes or novel candidate genes for CHD. In addition, the DNA may be analyzed for small pieces of extra or missing chromosomal DNA using a relatively new technology, whole-genome array comparative genomic hybridization (CGH). The investigators hypothesize that children with CHD have genetic abnormalities that are not detected by currently available genetic testing. This research will allow investigators to determine the frequency of subtle or cryptic genetic abnormalities in children with CHD. Identification of novel genetic causes of CHD will have important diagnostic and therapeutic consequences for these children.

Condition Intervention
Congenital Heart Disease
Other: Blood Sample Collection

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Genetics Testing of Individuals and Families With Congenital Heart Disease

Resource links provided by NLM:

Further study details as provided by Nationwide Children's Hospital:

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.

Estimated Enrollment: 1000
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Study Subjects
Individuals with Congenital Heart Disease and family members with or without Congenital Heart Disease
Other: Blood Sample Collection
Blood sample collection for direct sequencing, microarray, single nucleotide polymorphism, and/or whole-genome array comparative genomic hybridization DNA analyses

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. In addition, most of these discoveries have been limited to milder forms of CHD that have allowed for the generation of large kindreds.

The other modality involves the screening of large populations of children with sporadic (non-familial) cases of CHD for genetic abnormalities (nucleotide sequence variations or chromosomal copy number changes) in candidate genes for CHD. Studies using numerous species has led to the elucidation of the molecular pathways critical for normal cardiac development and also contributed to the identification of numerous genes necessary for this complex morphogenetic process. These discoveries have resulted in the generation of large number of candidate genes that may be responsible for CHD in humans (Srivastava and Olson, 2000). This approach has been successful in the identification of etiologic genes for CHD and when performed in a coordinated and careful manner will lead to significant advances in our understanding of the genetic contributors to CHD (Garg, 2006). In support of this approach, my laboratory has successfully used these screening approaches to identify novel genetic abnormalities in children with CHD (Schluterman, 2007; Richards, 2008; Ransom, 2009; Maitra, 2010).


Genders Eligible for Study:   Both
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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01192048

Contact: Vidu Garg, MD 614-355-3091

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
Principal Investigator: Vidu Garg, MD The Research Institute at Nationwide Children's Hospital
  More Information


Responsible Party: Vidu Garg, Investigator and Associate Professor, Nationwide Children's Hospital Identifier: NCT01192048     History of Changes
Other Study ID Numbers: IRB09-00339
Study First Received: August 30, 2010
Last Updated: February 21, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by 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

Additional relevant MeSH terms:
Heart Defects, Congenital
Heart Diseases
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities processed this record on May 26, 2015