Principal Investigator: Martin Tristani-Firouzi
Keywords: Genes , Genetics , Cardiology , Pediatric Department: Pediatric Administration
IRB Number: 00084861
Specialty: Pediatric Cardiology
Sub Specialties:
Recruitment Status: Active, not recruiting

Contact Information

Kristin Konery

Brief Summary

Study Aims
The Aims of this study are:

• Gene discovery of a comprehensive repertoire of genes responsible for CHD through genomic analyses including (but not limited to) copy-number variation, genome-wide association studies, whole exome sequencing, and whole genome sequencing,

• Identification of mutations responsible for CHD in large numbers of participants through sequencing of known CHD candidate genes,

• Genotype/Phenotype correlation of enrolled participants to determine how genetics influences the clinical outcome in CHD.

To accomplish this, the Consortium will develop and maintain a biorepository of specimens (DNA) and genetic data, along with detailed, phenotypic and clinical outcomes data in order to investigate relationships between genetic factors and phenotypic and clinical outcomes in congenital heart disease. Biospecimens and the derived genetic data will be shared with cardiovascular genetics researchers at participating Centers. Data will also be shared with investigators outside the Consortium consistent with NHLBI data-sharing policies. These biological samples will remain linked to detailed clinical data and will serve as a resource for long-term investigations into the genetic basis and clinical outcome of pediatric cardiovascular disorders beyond the current funding period. Through an increased understanding of the causes and modifiers of congenital heart disease, this initiative’s long-term goal is to enhance early detection, treatment and prevention of cardiovascular disease in newborns, children, and adults.


Genetic alterations contribute to both the etiology and the outcome of congenital heart disease.
To test this hypothesis, the investigators will recruit large numbers of subjects with sporadic as well as familial pediatric cardiovascular disorders (including adults with congenital heart disease) as well as subjects with normal heart structure and function who have a genotype strongly associated with CHD (such as Trisomy, or Chr22q deletion) from the participating Centers. Each consented participant and parents (and other family members when available) will donate biological specimens for banking and detailed phenotypic and clinical outcome data will be gathered. Analysis of these biospecimens will permit identification of genetic loci responsible for abnormal cardiovascular development. The identification of such genes and their modifiers will enhance understanding of both normal and abnormal cardiovascular development and will provide the foundation for investigations into the treatment and ultimately the prevention of cardiovascular anomalies. Furthermore, linking genetic information to clinical outcomes is expected to yield information that will facilitate risk stratification and improve treatment through individual genetically tailored regimens.


To address the gap in knowledge as to why some individuals with predisposing genotypes (e.g. trisomy, 22q11.2qdel or others) do not have CHD, we will derive induced pluripotent stem cells (iPSCs) from subjects with trisomy 21 (Down Syndrome) or 22q11.2qdel or others with and without CHD that we will differentiate into cardiomyocytes (iPSC-CMs). We plan to analyze cardiomyocyte gene expression between subjects with the same genotype (e.g., trisomy 21, 22q11.2qdel or others) who are discordant for CHD. We predict that the expression of genes not encoded in these mutated regions will be different. We expect that the identity of these modifiers and the pathways in which these participate may improve our understanding of the molecular mechanisms for normal and aberrant heart development.

Inclusion Criteria

While all patients with pediatric cardiovascular disease and adults with congenital heart disease are of interest, the study will initially focus on four CHD anatomic classifications:
• Atrial septal defects
• Conotruncal abnormalities
• Left-sided obstructive lesions
• Heterotaxy
• Additionally, subjects with CHD or subjects without CHD who have a genetic syndrome strongly associated with CHD (such as Trisomy or Chr22q deletion) will also be recruited.
Inclusion Criteria
• Age 0 – 99 years of age
• Males and females
• No ethnic or race restrictions
• Sporadic and familial cases will be screened
• Affected Individuals with CHD or subjects without CHD who have a genetic syndrome strongly associated with CHD ( such as Trisomy or Chr 22q deletion)

Exclusion Criteria

Exclusion Criteria
Patients who meet any of the following criteria will be excluded from the study:
• Lack of consent
Isolated patent foramen ovale
• Isolated prematurity-associated patent ductus arteriosus
• Lack of consent
• Isolated pulmonary stenosis secondary to twin-twin transfusion syndrome