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

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Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies. / Hempel, Maja; Casar Tena, Teresa; Diehl, Thilo; Burczyk, Martina S; Strom, Tim M; Kubisch, Christian; Philipp, Melanie; Lessel, Davor.

in: HUM GENET, Jahrgang 136, Nr. 3, 03.2017, S. 339-346.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Hempel, M, Casar Tena, T, Diehl, T, Burczyk, MS, Strom, TM, Kubisch, C, Philipp, M & Lessel, D 2017, 'Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies', HUM GENET, Jg. 136, Nr. 3, S. 339-346. https://doi.org/10.1007/s00439-017-1762-2

APA

Hempel, M., Casar Tena, T., Diehl, T., Burczyk, M. S., Strom, T. M., Kubisch, C., Philipp, M., & Lessel, D. (2017). Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies. HUM GENET, 136(3), 339-346. https://doi.org/10.1007/s00439-017-1762-2

Vancouver

Hempel M, Casar Tena T, Diehl T, Burczyk MS, Strom TM, Kubisch C et al. Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies. HUM GENET. 2017 Mär;136(3):339-346. https://doi.org/10.1007/s00439-017-1762-2

Bibtex

@article{efa8a84c7f494f54a499416f0811a9ec,
title = "Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies",
abstract = "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.",
keywords = "Journal Article",
author = "Maja Hempel and {Casar Tena}, Teresa and Thilo Diehl and Burczyk, {Martina S} and Strom, {Tim M} and Christian Kubisch and Melanie Philipp and Davor Lessel",
year = "2017",
month = mar,
doi = "10.1007/s00439-017-1762-2",
language = "English",
volume = "136",
pages = "339--346",
journal = "HUM GENET",
issn = "0340-6717",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies

AU - Hempel, Maja

AU - Casar Tena, Teresa

AU - Diehl, Thilo

AU - Burczyk, Martina S

AU - Strom, Tim M

AU - Kubisch, Christian

AU - Philipp, Melanie

AU - Lessel, Davor

PY - 2017/3

Y1 - 2017/3

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1007/s00439-017-1762-2

DO - 10.1007/s00439-017-1762-2

M3 - SCORING: Journal article

C2 - 28180938

VL - 136

SP - 339

EP - 346

JO - HUM GENET

JF - HUM GENET

SN - 0340-6717

IS - 3

ER -