PuSH - Publication Server of Helmholtz Zentrum München: Compound <em>heterozygous GATA5</em> mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Hempel, M.* ; Casar Tena, T.* ; Diehl, T.* ; Burczyk, M.S.* ; Strom, T.M. ; Kubisch, C.* ; Philipp, M.* ; Lessel, D.*

Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies.

Hum. Genet. 136, 339-346 (2017)

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

GATA5 belongs to the GATA family of transcription factors characterized by highly evolutionarily conserved zinc-finger DNA-binding domains. Mouse models have implicated a role of GATA5 during mammalian embryogenesis, including proper heart development and gender-specific regulation of female genitourinary tract formation. Previous studies have found an association of heterozygous missense alterations in GATA5 with a broad variety of heart diseases; however, the clinical relevance of the identified susceptibility variants has remained unclear. Here, we report on a girl with hydrops fetalis, congenital heart defects, clitoromegaly and postnatally increased 17-hydroxyprogesterone levels. By trio whole-exome sequencing, we identified compound heterozygous missense mutations, p.Ser19Trp and p.Arg202Gln, in GATA5 as putative disease-causing alterations. The identified mutations fail to rescue the cardia bifida phenotype in a zebrafish model, mislocalize to subnuclear foci when transiently transfected in HEK293 cells and possess less transcriptional activity. In addition to demonstrating the pathogenicity of identified mutations, our findings show that GATA5 mutations, in addition to heart diseases, can result in congenital abnormalities of the female genitourinary tract in humans.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Bicuspid Aortic-valve; Of-function Mutation; Sequence Variants; Gene-expression; Nuclear-bodies; Zebrafish; Mice; Differentiation; Activation; Endoderm

ISSN (print) / ISBN 0340-6717

e-ISSN 1432-1203

Journal Human Genetics

Quellenangaben Volume: 136, Issue: 3, Pages: 339-346

Publisher Springer

Publishing Place New York

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Human Genetics (IHG)