Document Detail

Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia.
MedLine Citation:
PMID:  23138528     Owner:  NLM     Status:  MEDLINE    
Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm occurring as either an isolated defect or in association with other anomalies. Genetic factors including aneuploidies and copy number variants are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we used whole exome sequencing (WES) to identify a paternally inherited novel missense GATA4 variant (c.754C>T; p.R252W) in a familial case of CDH with incomplete penetrance. Phenotypic characterization of the family included magnetic resonance imaging of the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the two "unaffected" missense variant carriers. Screening 96 additional CDH patients identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non-isolated CDH patient. In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH.
Lan Yu; Julia Wynn; Yee Him Cheung; Yufeng Shen; George B Mychaliska; Timothy M Crombleholme; Kenneth S Azarow; Foong Yen Lim; Dai H Chung; Douglas Potoka; Brad W Warner; Brian Bucher; Charles Stolar; Gudrun Aspelund; Marc S Arkovitz; Wendy K Chung
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-09
Journal Detail:
Title:  Human genetics     Volume:  132     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-12     Completed Date:  2013-03-29     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  285-92     Citation Subset:  IM    
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MeSH Terms
DNA Copy Number Variations / genetics*
Exome / genetics*
GATA4 Transcription Factor / genetics*
Genetic Variation
Genome-Wide Association Study
Hernia, Diaphragmatic / congenital*,  genetics
Infant, Newborn
Mutation, Missense*
Polymorphism, Single Nucleotide*
Sequence Analysis, DNA
Grant Support
Reg. No./Substance:
0/GATA4 Transcription Factor; 0/GATA4 protein, human

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