How to cite this article: Wat MJ, Shchelochkov OA, Holder AM, Breman AM, Dagli A, Bacino C, Scaglia F, Zori RT, Cheung SW, Scott DA, Kang S-HL. 2009. Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia. Am J Med Genet Part A 149A:1661–1677.
Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia†
Version of Record online: 15 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 8, pages 1661–1677, August 2009
How to Cite
Wat, M. J., Shchelochkov, O. A., Holder, A. M., Breman, A. M., Dagli, A., Bacino, C., Scaglia, F., Zori, R. T., Cheung, S. W., Scott, D. A. and Kang, S.-H. L. (2009), Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia. Am. J. Med. Genet., 149A: 1661–1677. doi: 10.1002/ajmg.a.32896
- Issue online: 23 JUL 2009
- Version of Record online: 15 JUL 2009
- Manuscript Accepted: 2 APR 2009
- Manuscript Received: 22 DEC 2008
- NIH. Grant Number: HD-050583
- congenital heart defects;
- 8p23.1 deletion syndrome;
- diaphragmatic hernia;
- array comparative genomic hybridization;
- prenatal diagnosis
Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genomic hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm. © 2009 Wiley-Liss, Inc.