Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH).
OBJECTIVE
Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH.


METHODS
We have designed a custom array targeted at genes and genomic loci associated with CDH. A total of 79 isolated CDH patients were screened using this targeted array.


RESULTS
In three patients, we detected genomic imbalances associated with the observed diaphragmatic hernia; a deletion of 8p22-p23.3, 14.2 Mb in size, a 340 kb duplication of Xq13.1 including the ephrin-B1 gene (EFNB1), and mosaicism for trisomy 2.


CONCLUSIONS
Using this approach, we detected genomic imbalances associated with CDH in 3/79 (4%) isolated CDH patients. Our findings further implicate 8p deletions as being associated with CDH. The duplication of EFNB1 further highlights this gene as a potential candidate involved in diaphragm development. Mosaicism for trisomy 2 is a rare event and unlikely to be a common cause of CDH. Further investigations of isolated CDH patients by array CGH will continue to identify novel submicroscopic loci and refine genomic regions associated with CDH.
Centre for Human Genetics, KU Leuven, Leuven, Belgium.
Kasemsri
K
Srisupundit
Paul D
PD
Brady
Koenraad
K
Devriendt
Jean-Pierre
JP
Fryns
Rogelio
R
Cruz-Martinez
Eduard
E
Gratacos
Jan A
JA
Deprest
Joris R
JR
Vermeesch
D022981:Allelic Imbalance / Q000502:physiology*; D000653:Amniotic Fluid / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D006548:Hernia, Diaphragmatic / Q000235:genetics*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods