Author + information
- Thor Thorsson,
- S. Sow,
- J. Levine,
- WW Russell,
- N. El-Kashlam,
- Jeffrey Innis,
- S. Zoellner and
- Mark Russell
Congenital cardiac defects (CCD) represent the most common group of birth defects, estimated at 8 per 1000 births. Genetic characterization of patients and families with cardiac defects has identified a number of genes required for heart development. Yet, mutations affecting known genes still account for only a small fraction of CCD suggesting that many more genes and developmental mechanisms remain to be identified. This study aimed at identifying novel loci containing genes critical for human cardiac development using duplication/deletion mapping.
We reviewed 766 described cases of patients with significant chromosomal rearrangements who were determined to have a chromosomal abnormality. Patients with multiple or whole chromosomal defects were excluded. Patients with overlapping deletions and/or duplications were grouped to identify regions potentially involved in heart development.
36 chromosomal regions were identified in which 5 or more patients had overlapping rearrangements and 99 loci were affected in 2-4 patients with overlapping rearrangements. Of the former group, 9 of 36 loci involve genes (NKX2-5, GATA4, TBX1, GJA5, TAB2, NOTCH1, HAND2, CHD7, EHMT1) known to be involved in heart development, 9 involved deleted regions previously proposed to be involved in heart development, and 18 were novel loci or loci not strongly associated with cardiac defects. Of the 99 loci affected in 2-4 patients, only 11 involved loci were known or suspected to be associated with congenital heart defects. The 22q13.2 locus was further refined based on a new microdeletion to restrict the number of candidate genes to BIK and PACSIN2 which may represent a novel candidate gene/genes for CCD.
Duplication/deletion mapping of chromosomal rearrangements associated with CCD will provide an important roadmap for genome-wide sequencing and genetic mapping strategies to identify novel genes critical for heart development. The variable incidence of cardiac defects across loci suggests a dependence on genetic and/or environmental modifiers to determine the penetrance and phenotypic expression of the observed variations in the copy number of the candidate genes.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Congenital Cardiology Solutions: Congenital Electrophysiology and Genetics
Abstract Category: 13. Congenital Cardiology Solutions: Pediatric
Presentation Number: 1247-129
- 2013 American College of Cardiology Foundation