RT Journal Article
SR Electronic
T1 De novo copy number variants are associated with congenital diaphragmatic hernia
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 650
OP 659
DO 10.1136/jmedgenet-2012-101135
VO 49
IS 10
A1 Lan Yu
A1 Julia Wynn
A1 Lijiang Ma
A1 Saurav Guha
A1 George B Mychaliska
A1 Timothy M Crombleholme
A1 Kenneth S Azarow
A1 Foong Yen Lim
A1 Dai H Chung
A1 Douglas Potoka
A1 Brad W Warner
A1 Brian Bucher
A1 Charles A LeDuc
A1 Katherine Costa
A1 Charles Stolar
A1 Gudrun Aspelund
A1 Marc S Arkovitz
A1 Wendy K Chung
YR 2012
UL http://jmg.bmj.com/content/49/10/650.abstract
AB Background Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Although the aetiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Chromosomal anomalies have been reported in CDH. Methods In this study, the authors investigated the frequency of chromosomal anomalies and copy number variants (CNVs) in 256 parent–child trios of CDH using clinical conventional cytogenetic and microarray analysis. The authors also selected a set of CDH related training genes to prioritise the genes in those segmental aneuploidies and identified the genes and gene sets that may contribute to the aetiology of CDH. Results The authors identified chromosomal anomalies in 16 patients (6.3%) of the series including three aneuploidies, two unbalanced translocation, and 11 patients with de novo CNVs ranging in size from 95 kb to 104.6 Mb. The authors prioritised the genes in the CNV segments and identified KCNA2, LMNA, CACNA1S, MYOG, HLX, LBR, AGT, GATA4, SOX7, HYLS1, FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, HOMER2, BNC1, BID, and TBX1 as genes that may be involved in diaphragm development. Gene enrichment analysis identified the most relevant gene ontology categories as those involved in tissue development (p=4.4×10−11) or regulation of multicellular organismal processes (p=2.8×10−10) and ‘receptor binding’ (p=8.7×10−14) and ‘DNA binding transcription factor activity’ (p=4.4×10−10). Conclusions The present findings support the role of chromosomal anomalies in CDH and provide a set of candidate genes including FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, SOX7, BNC1, BID, and TBX1 for further analysis in CDH.