A novel TBX1 missense mutation in patients with syndromic congenital heart defects

Jaouadi, Amel; Tabebi, Mouna; Abdelhedi, Fatma; Abid, Dorra; Kamoun, Fatma; Chabchoub, I.; Maatoug, S.; Doukali, Hajer; Belghuith, Neila; Ksentini, Mohamed; Keskes, Leila; Triki, Chahnez; Hachicha, M.; Kamoun, S.; Kamoun, Hassen

doi:10.1016/j.bbrc.2018.03.190

Cited by 12 publications

(7 citation statements)

References 21 publications

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“…CHD is one of the most well-known congenital deficiencies. The occurrence of CHD is associated with complex genetic factors and teratogenic factors in the environment during the first 3 months of pregnancy and during the second to seventh weeks of gestation [40][41][42]. However, less than 50% of the causes of CHD have been identified thus far [5], and it is still of great clinical value to investigate the aetiology and pathogenesis of CHD.…”

Section: Discussionmentioning

confidence: 99%

The TBX1/miR-193a-3p/TGF-β2 Axis Mediates CHD by Promoting Ferroptosis

Yang

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Congenital heart disease (CHD) is the most common noninfectious cause of death during the neonatal stage. T-box transcription factor 1 (TBX1) is the main genetic determinant of 22q11.2 deletion syndrome (22q11.2DS), which is a common cause of CHD. Moreover, ferroptosis is a newly discovered kind of programmed cell death. In this study, the interaction among TBX1, miR-193a-3p, and TGF-β2 was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and dual-luciferase reporter assays. TBX1 silencing was found to promote TGF-β2 messenger ribonucleic acid (mRNA) and protein expression by downregulating the miR-193a-3p levels in H9c2 cells. In addition, the TBX1/miR-193a-3p/TGF-β2 axis was found to promote ferroptosis based on assessments of lipid reactive oxygen species (ROS) levels, Fe2+ concentrations, mitochondrial ROS levels, and malondialdehyde (MDA) contents; Cell Counting Kit-8 (CCK-8) assays and transmission electron microscopy; and Western blotting analysis of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), NADPH oxidase 4 (NOX4), and acyl-CoA synthase long-chain family member 4 (ACSL4) protein expression. The protein expression of NRF2, GPX4, HO-1, NOX4, and ACSL4 and the level of MDA in human CHD specimens were also detected. In addition, TBX1 and miR-193a-3p expression was significantly downregulated and TGF-β2 levels were high in human embryonic CHD tissues, as indicated by the H9c2 cell experiments. In summary, the TBX1/miR-193a-3p/TGF-β2 axis mediates CHD by inducing ferroptosis in cardiomyocytes. TGF-β2 may be a target gene for CHD diagnosis and treatment in children.

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Section: Discussionmentioning

confidence: 99%

The TBX1/miR-193a-3p/TGF-β2 Axis Mediates CHD by Promoting Ferroptosis

Yang

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…TBX1 has been extensively studied in murine models in which the alteration of this gene is associated with cardiovascular, thymic, and parathyroid defects, a phenotype that is similar to the one seen in 22q11 deletion [98]. Recent studies in humans have detected new mutations that could explain the clinical spectrum of the syndrome [99]. The estimated prevalence varies from 1:4000 to 1:6000 without sex or ethnic differences [100].…”

Section: Digeorge Syndrome (Dgs)mentioning

confidence: 99%

Primary immunodeficiency and autoimmunity: A comprehensive review

Amaya-Uribe

Rojas

Azizi

et al. 2019

Journal of Autoimmunity

148

120

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“…The well-established environmental factors underlying CHD include maternal conditions (such as innutrition, viral infection and endocrine disorder) and exposures to toxic chemicals, therapeutic drugs, or ionizing radiation during pregnancy (Patel and Burns, 2013). However, increasing studies underscore the genetic defects underpinning CHD, and variations in over 70 genes, encompassing those encoding transcription factors, signaling molecules, and sarcomeric proteins, have been involved in CHD (Bashamboo et al, 2018;Cantù et al, 2018;Jaouadi et al, 2018;Li et al, 2018a,c;Lombardo et al, 2018;Manheimer et al, 2018;Pierpont et al, 2018;Razmara and Garshasbi, 2018;Stephen et al, 2018;Xu et al, 2018;Yu Z et al, 2018;Alankarage et al, 2019;Gao et al, 2019;Kalayinia et al, 2019Kalayinia et al, , 2020Ma et al, 2019;Wang J et al, 2019, Wang Z et al, 2019Watkins et al, 2019;Zhu et al, 2019;Faucherre et al, 2020;Shabana et al, 2020;Zhao et al, 2020). Among the recognized CHD-causative genes, the majority code for cardiac transcription factors, encompassing TBX5, GATA4, and NKX2-5 (Li and Yang, 2017).…”

Section: Introductionmentioning

confidence: 99%