RGD Reference Report - GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. - Rat Genome Database

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GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve.

Authors: Shi, Lin-Mei  Tao, Ju-Wei  Qiu, Xing-Biao  Wang, Juan  Yuan, Fang  Xu, Lei  Liu, Hua  Li, Ruo-Gu  Xu, Ying-Jia  Wang, Qian  Zheng, Hong-Zhen  Li, Xin  Wang, Xiao-Zhou  Zhang, Min  Qu, Xin-Kai  Yang, Yi-Qing 
Citation: Shi LM, etal., Int J Mol Med. 2014 May;33(5):1219-26. doi: 10.3892/ijmm.2014.1700. Epub 2014 Mar 14.
RGD ID: 155260354
Pubmed: PMID:24638895   (View Abstract at PubMed)
DOI: DOI:10.3892/ijmm.2014.1700   (Journal Full-text)

Bicuspid aortic valve (BAV) is the most common form of congenital cardiovascular defect in humans worldwide and is responsible for substantial morbidity and mortality. Accumulating evidence has demonstated that genetic risk factors are involved in the pathogenesis of BAV. However, BAV is genetically heterogeneous and the genetic basis underlying BAV in a large number of patients remains unknown. In the present study, the coding regions and splice junction sites of the GATA5 gene, which codes for a zinc-finger transcription factor crucial for the normal development of the aortic valve, was sequenced initially in 110 unrelated patients with BAV. The available relatives of the mutation carriers and 200 unrelated healthy individuals used as controls were subsequently genotyped for GATA5. The functional effect of the mutations was characterized by using a luciferase reporter assay system. As a result, two novel heterozygous GATA5 mutations, p.Y16D and p.T252P, were identified in two families with autosomal dominant inheritance of BAV, respectively. The variations were absent in 400 control chromosomes and the altered amino acids were completely conserved evolutionarily. Functional assays revealed that the two GATA5 mutants were associated with significantly reduced transcriptional activity compared with their wild-type counterpart. To the best of our knowledge, this is the first study on the association of GATA5 loss-of-function mutations with enhanced susceptibility to BAV, providing novel insight into the molecular mechanism involved in human BAV and suggesting a potential role for the early prophylaxis and personalized treatment of this common congenital heart disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bicuspid aortic valve disease  IAGP 155260354DNA:mutations:cds:c.46T>G (p.Y16D), c.754A>C ((p.T252P)(human)RGD 
bicuspid aortic valve disease  ISOGATA5 (Homo sapiens)155260354; 155260354DNA:mutations:cds:c.46T>G (p.Y16D), c.754A>C ((p.T252P)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gata5  (GATA binding protein 5)

Genes (Mus musculus)
Gata5  (GATA binding protein 5)

Genes (Homo sapiens)
GATA5  (GATA binding protein 5)


Additional Information