TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy

Biochemical and Biophysical Research Communications
Xian-Ling ZhangYi-Qing Yang

Abstract

The cardiac T-box transcription factor TBX5 is crucial for proper cardiovascular development, and mutations in TBX5 have been associated with various congenital heart diseases and arrhythmias in humans. However, whether mutated TBX5 contributes to dilated cardiomyopathy (DCM) remains unclear. In this study, the coding exons and flanking introns of the TBX5 gene were sequenced in 190 unrelated patients with idiopathic DCM. The available family members of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX5. The functional characteristics of the mutant TBX5 were explored in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.S154A, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 control chromosomes and the altered amino acid was completely conserved evolutionarily across various species. Functional assays revealed that the mutant TBX5 had significantly decreased transcriptional activity. Furthermore, the mutation...Continue Reading

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Citations

Feb 6, 2016·Journal of the American College of Cardiology·Rowida AlmomaniIngrid M B H van de Laar
May 13, 2015·International Journal of Molecular Medicine·Wei ZhouXing-Biao Qiu
Jun 30, 2015·Clinical Chemistry and Laboratory Medicine : CCLM·Cui-Mei ZhaoYi-Qing Yang
Sep 22, 2016·Molecular Genetics & Genomic Medicine·Martina DreßenMarkus Krane
Oct 25, 2016·International Journal of Cardiology·Alexandra Pérez-SerraOscar Campuzano
Sep 14, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Fang YuanYi-Qing Yang
Feb 16, 2018·Heart and Vessels·Yu-Min SunYi-Qing Yang
Sep 7, 2017·Circulation Research·Kuei-Ting ChangGuey-Shin Wang
Mar 2, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nadine A KasparianEdwin P E Kirk
Jan 19, 2017·Clinical Chemistry and Laboratory Medicine : CCLM·Xing-Biao QiuYi-Qing Yang
Nov 19, 2015·Clinical Chemistry and Laboratory Medicine : CCLM·Yi-Meng ZhouYi-Qing Yang
Dec 13, 2016·Pediatric Cardiology·Juan WangYi-Qing Yang
Dec 12, 2018·Journal of Cardiovascular Translational Research·Ying-Jia XuYi-Qing Yang
May 1, 2018·Journal of Cardiovascular and Thoracic Research·Mehri KhatamiRazieh Zare Bidaki
Apr 2, 2016·Molecular Medicine Reports·Dong-Feng GuoXing-Biao Qiu
Jul 11, 2021·Heart Failure Reviews·Prerna GiriBhagyalaxmi Mohapatra

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