Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia

Hum Mol Genet. 2007 Feb 15;16(4):424-30. doi: 10.1093/hmg/ddl475. Epub 2007 Jan 8.


Non-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that is often caused by de novo chromosomal anomalies. In this report, we use genome-wide oligonucleotide-based array comparative genome hybridization (aCGH) followed by rapid real-time quantitative PCR analysis to identify, confirm and map chromosomal anomalies in a cohort of 26 CDH+ patients. One hundred and five putative copy number changes were identified by aCGH in our cohort of CDH+ patients. Sixty-one of these changes (58%) had been previously described in normal controls. Twenty of the remaining 44 changes (45%) were confirmed by quantitative real-time PCR or standard cytogenetic techniques. These changes included de novo chromosomal abnormalities in five of the 26 patients (19%), two of whom had previously normal G-banded chromosome analyses. Data from these patients provide evidence for the existence of CDH-related genes on chromosomes 2q37, 6p22-25 and 14q, and refine the CDH minimal deleted region on 15q26 to an interval that contains COUP-TFII and only eight other known genes. Although COUP-TFII is likely to play a role in the development of CDH in patients with 15q26 deletions, we did not find COUP-TFII mutations in 73 CDH samples. We conclude that the combination of oligonucleotide-based aCGH and quantitative real-time PCR is an effective method of identifying, confirming and mapping clinically relevant copy number changes in patients with CDH+. This method is more sensitive than G-banded chromosome analysis and may find wide application in screening patients with congenital anomalies.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Aberrations
  • Chromosome Banding
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 6
  • Female
  • Gene Dosage
  • Gene Expression Profiling
  • Genetic Testing
  • Genome, Human*
  • Hernia, Diaphragmatic / genetics*
  • Hernias, Diaphragmatic, Congenital*
  • Humans
  • Male
  • Nucleic Acid Hybridization / methods*
  • Oligonucleotide Array Sequence Analysis*