Frontiers in Genetics (Mar 2023)
Case report: Novel TBX5-related pathogenic mechanism of Holt–Oram syndrome
- Yuheng Lang,
- Yuheng Lang,
- Yuheng Lang,
- Yuheng Lang,
- Yuheng Lang,
- Yue Zheng,
- Yue Zheng,
- Yue Zheng,
- Yue Zheng,
- Yue Zheng,
- Bingcai Qi,
- Bingcai Qi,
- Bingcai Qi,
- Bingcai Qi,
- Weifeng Zheng,
- Weifeng Zheng,
- Weifeng Zheng,
- Weifeng Zheng,
- Chengxiu Zhao,
- Hu Zhai,
- Hu Zhai,
- Hu Zhai,
- Hu Zhai,
- Gang Wang,
- Gang Wang,
- Gang Wang,
- Gang Wang,
- Zhiqiang Luo,
- Zhiqiang Luo,
- Zhiqiang Luo,
- Zhiqiang Luo,
- Tong Li,
- Tong Li,
- Tong Li,
- Tong Li,
- Tong Li
Affiliations
- Yuheng Lang
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Yuheng Lang
- School of Medicine, Nankai University, Tianjin, China
- Yuheng Lang
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Yuheng Lang
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Yuheng Lang
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Yue Zheng
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Yue Zheng
- School of Medicine, Nankai University, Tianjin, China
- Yue Zheng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Yue Zheng
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Yue Zheng
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Bingcai Qi
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Bingcai Qi
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Bingcai Qi
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Bingcai Qi
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Weifeng Zheng
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Weifeng Zheng
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Weifeng Zheng
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Weifeng Zheng
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Chengxiu Zhao
- Department of Anesthesiology, Handan First Hospital, Handan, China
- Hu Zhai
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Hu Zhai
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Hu Zhai
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Hu Zhai
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Gang Wang
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Gang Wang
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Gang Wang
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Gang Wang
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Zhiqiang Luo
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Zhiqiang Luo
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Zhiqiang Luo
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Zhiqiang Luo
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- Tong Li
- Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China
- Tong Li
- School of Medicine, Nankai University, Tianjin, China
- Tong Li
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Tong Li
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tong Li
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- DOI
- https://doi.org/10.3389/fgene.2023.1063202
- Journal volume & issue
-
Vol. 14
Abstract
Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS.Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3′-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells.Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.
Keywords
