Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia

Lan Yu, Julia Wynn, Yee Him Cheung, Yufeng Shen, George B. Mychaliska, Timothy M. Crombleholme, Kenneth Azarow, Foong Yen Lim, Dai H. Chung, Douglas Potoka, Brad W. Warner, Brian Bucher, Charles Stolar, Gudrun Aspelund, Marc S. Arkovitz, Wendy K. Chung

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)285-292
Number of pages8
JournalHuman Genetics
Volume132
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Fingerprint

Exome
Diaphragm
Congenital Diaphragmatic Hernias
Penetrance
Aneuploidy
Abdomen
Thorax
Magnetic Resonance Imaging
Genes
Paternal Inheritance

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Yu, L., Wynn, J., Cheung, Y. H., Shen, Y., Mychaliska, G. B., Crombleholme, T. M., ... Chung, W. K. (2013). Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. Human Genetics, 132(3), 285-292. https://doi.org/10.1007/s00439-012-1249-0

Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. / Yu, Lan; Wynn, Julia; Cheung, Yee Him; Shen, Yufeng; Mychaliska, George B.; Crombleholme, Timothy M.; Azarow, Kenneth; Lim, Foong Yen; Chung, Dai H.; Potoka, Douglas; Warner, Brad W.; Bucher, Brian; Stolar, Charles; Aspelund, Gudrun; Arkovitz, Marc S.; Chung, Wendy K.

In: Human Genetics, Vol. 132, No. 3, 03.2013, p. 285-292.

Research output: Contribution to journalArticle

Yu, L, Wynn, J, Cheung, YH, Shen, Y, Mychaliska, GB, Crombleholme, TM, Azarow, K, Lim, FY, Chung, DH, Potoka, D, Warner, BW, Bucher, B, Stolar, C, Aspelund, G, Arkovitz, MS & Chung, WK 2013, 'Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia', Human Genetics, vol. 132, no. 3, pp. 285-292. https://doi.org/10.1007/s00439-012-1249-0
Yu L, Wynn J, Cheung YH, Shen Y, Mychaliska GB, Crombleholme TM et al. Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. Human Genetics. 2013 Mar;132(3):285-292. https://doi.org/10.1007/s00439-012-1249-0
Yu, Lan ; Wynn, Julia ; Cheung, Yee Him ; Shen, Yufeng ; Mychaliska, George B. ; Crombleholme, Timothy M. ; Azarow, Kenneth ; Lim, Foong Yen ; Chung, Dai H. ; Potoka, Douglas ; Warner, Brad W. ; Bucher, Brian ; Stolar, Charles ; Aspelund, Gudrun ; Arkovitz, Marc S. ; Chung, Wendy K. / Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. In: Human Genetics. 2013 ; Vol. 132, No. 3. pp. 285-292.
@article{b3c9fd5d36974f4dada8afb41cd18dfa,
title = "Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia",
abstract = "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.",
author = "Lan Yu and Julia Wynn and Cheung, {Yee Him} and Yufeng Shen and Mychaliska, {George B.} and Crombleholme, {Timothy M.} and Kenneth Azarow and Lim, {Foong Yen} and Chung, {Dai H.} and Douglas Potoka and Warner, {Brad W.} and Brian Bucher and Charles Stolar and Gudrun Aspelund and Arkovitz, {Marc S.} and Chung, {Wendy K.}",
year = "2013",
month = "3",
doi = "10.1007/s00439-012-1249-0",
language = "English (US)",
volume = "132",
pages = "285--292",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia

AU - Yu, Lan

AU - Wynn, Julia

AU - Cheung, Yee Him

AU - Shen, Yufeng

AU - Mychaliska, George B.

AU - Crombleholme, Timothy M.

AU - Azarow, Kenneth

AU - Lim, Foong Yen

AU - Chung, Dai H.

AU - Potoka, Douglas

AU - Warner, Brad W.

AU - Bucher, Brian

AU - Stolar, Charles

AU - Aspelund, Gudrun

AU - Arkovitz, Marc S.

AU - Chung, Wendy K.

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84875606307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875606307&partnerID=8YFLogxK

U2 - 10.1007/s00439-012-1249-0

DO - 10.1007/s00439-012-1249-0

M3 - Article

VL - 132

SP - 285

EP - 292

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 3

ER -