Case report: Novel TBX5-related pathogenic mechanism of Holt-Oram syndrome

Yuheng Lang; Yue Zheng; Bingcai Qi; Weifeng Zheng; Chengxiu Zhao; Hu Zhai; Gang Wang; Zhiqiang Luo; Tong Li

doi:10.3389/fgene.2023.1063202

Case report: Novel TBX5-related pathogenic mechanism of Holt-Oram syndrome

Front Genet. 2023 Mar 1:14:1063202. doi: 10.3389/fgene.2023.1063202. eCollection 2023.

Authors

Yuheng Lang^{1

2

3

4

5}, Yue Zheng^{1

2

3

4

5}, Bingcai Qi^{1

3

4

5}, Weifeng Zheng^{1

3

4

5}, Chengxiu Zhao⁶, Hu Zhai^{1

3

4

5}, Gang Wang^{1

3

4

5}, Zhiqiang Luo^{1

3

4

5}, Tong Li^{1

2

3

4

5}

Affiliations

¹ Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China.
² School of Medicine, Nankai University, Tianjin, China.
³ Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.
⁴ Artificial Cell Engineering Technology Research Center, Tianjin, China.
⁵ Tianjin Institute of Hepatobiliary Disease, Tianjin, China.
⁶ Department of Anesthesiology, Handan First Hospital, Handan, China.

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: ChIP; Holt–Oram syndrome; SNP; Tbx5; case report.

Publication types

Case Reports

Grants and funding

This work was funded by the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-035A), Tianjin “Project + Team” Key Training Special Project (no. XC202040), Tianjin “131” Innovative Talent Team Project (no. 201939), Key Project of Tianjin Natural Science Foundation (no. 21JCZDJC00240), Tianjin Municipal Health and Health Committee Science and Technology Project (no. ZD20001), Tianjin Health Committee Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Project (no. 2021139), Hebei Provincial Health Committee Project (no. 20220676), Hebei Provincial Health and Family Planning Committee Key Medical Science Research Project (no. 20171087), and Tianjin Municipal Health and Health Committee Science and Technology Talent Cultivation Project (no. KJ20008).