Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks

Mauro Longoni, Kasper Lage, Meaghan K. Russell, Maria Loscertales, Omar A. Abdul-Rahman, Gareth Baynam, Steven B. Bleyl, Paul D. Brady, Jeroen Breckpot, Chih P. Chen, Koenraad Devriendt, Gabriele Gillessen-Kaesbach, Arthur W. Grix, Alan F. Rope, Osamu Shimokawa, Bernarda Strauss, Dagmar Wieczorek, Elaine H. Zackai, Caroline M. Coletti, Faouzi I. MaaloufKristin M. Noonan, Ji H. Park, Adam A. Tracy, Charles Lee, Patricia K. Donahoe, Barbara R. Pober

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high-resolution arrays in patients who carry a loss (n=18) or a gain (n=1) of sub-band 8p23.1. We confirm a region involved in both diaphragmatic and heart malformations. Results from a novel CNVConnect algorithm, prioritizing protein-protein interactions between products of genes in the 8p23.1 hotspot and products of previously known CDH causing genes, implicated GATA4, NEIL2, and SOX7 in diaphragmatic defects. Sequence analysis of these genes in 226 chromosomally normal CDH patients, as well as in a small number of deletion 8p23.1 patients, showed rare unreported variants in the coding region; these may be contributing to the diaphragmatic phenotype. We also demonstrated that two of these three genes were expressed in the E11.5-12.5 primordial mouse diaphragm, the developmental stage at which CDH is thought to occur. This combination of bioinformatics and expression studies can be applied to other chromosomal hotspots, as well as private microdeletions or microduplications, to identify causative genes and their interaction networks.

Original languageEnglish (US)
Pages (from-to)3148-3158
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number12
StatePublished - Dec 2012
Externally publishedYes


  • CNVConnect
  • Congenital diaphragmatic hernia
  • Congenital heart defect
  • DNA copy number variants
  • Deletion 8p23 1
  • Duplication 8p23 1
  • GATA4
  • NEIL2
  • SOX7

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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