This is a preview of subscription content, access via your institution
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Data generated as part of this study are available from the corresponding author upon reasonable request.
Vivante A, Kleppa MJ, Schulz J, Kohl S, Sharma A, Chen J, et al. Mutations in TBX18 cause dominant urinary tract malformations via transcriptional dysregulation of ureter development. Am J Hum Genet. 2015;97:291–301.
Ovejero D, Garcia-Giralt N, Martínez-Gil N, Rabionet R, Balcells S, Grinberg D, et al. Clinical description and genetic analysis of a novel familial skeletal dysplasia characterized by high bone mass and lucent bone lesions. Bone. 2022;161:116450.
Papaioannou VE. The T-box gene family: emerging roles in development, stem cells and cancer. Development. 2014;141:3819–33.
Greulich F, Rudat C, Kispert A. Mechanisms of T-box gene function in the developing heart. Cardiovasc Res. 2011;91:212–22.
Wiese C, Grieskamp T, Airik R, Mommersteeg MTM, Gardiwal A, de Gier-de Vries C, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 2009;104:388–97.
Yang M, Zhang GG, Wang T, Wang X, Tang YH, Huang H, et al. TBX18 gene induces adipose-derived stem cells to differentiate into pacemaker-like cells in the myocardial microenvironment. Int J Mol Med. 2016;38:1403–10.
Wu SP, Dong XR, Regan JN, Su C, Majesky MW. Tbx18 regulates development of the epicardium and coronary vessels. Dev Biol. 2013;383:307–20.
Greulich F, Trowe MO, Leffler A, Stoetzer C, Farin HF, Kispert A. Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature. J Mol Cell Cardiol. 2016;97:140–9.
Ma L, Li J, Liu Y, Pang S, Huang W, Yan B. Novel and functional variants within the TBX18 gene promoter in ventricular septal defects. Mol Cell Biochem. 2013;382:121–6.
Engwerda A, Frentz B, den Ouden AL, Flapper BCT, Swertz MA, Gerkes EH, et al. The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports. Eur J Hum Genet. 2018;26:1478–89.
Herkert JC, Abbott KM, Birnie E, Meems-Veldhuis MT, Boven LG, Benjamins M, et al. Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy. Genet Med. 2018;20:1374–86.
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.
Samocha KE, Robinson EB, Sanders SJ, Stevens C, Sabo A, McGrath LM, et al. A framework for the interpretation of de novo mutation in human disease. Nat Genet. 2014;46:944–50.
van der Velde KJ, de Boer EN, van Diemen CC, Sikkema-Raddatz B, Abbott KM, Knopperts A, et al. GAVIN: Gene-Aware Variant INterpretation for medical sequencing. Genome Biol. 2017;18:6.
Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310–5.
Clowes C, Boylan MG, Ridge LA, Barnes E, Wright JA, Hentges KE. The functional diversity of essential genes required for mammalian cardiac development. Genesis. 2014;52:713–37.
We would like to thank all patients involved. We also thank Kate Mc Intyre for editing the manuscript, Ludolf Boven for assisting in the lab and Jan Jongbloed for assisting in patient selection.
This work was supported by a grant from ZonMw (113312101) and by crowdfunding organised by Chromosome 6 parents. AE is the recipient of a Junior Scientific Masterclass MD/PhD scholarship from the University Medical Center Groningen.
The authors declare no competing interests.
Ethics approval and consent to participate
The study design for Sanger sequencing was discussed with the accredited Medical Ethics Review Committee of the University Medical Centre Groningen. The committee waived full ethical evaluation. All the patients in this clinical cohort consented to use of residual material and data.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Engwerda, A., Abbott, K.M., Hitzert, M.M. et al. The role of TBX18 in congenital heart defects in humans not confirmed. Eur J Hum Genet 31, 138–141 (2023). https://doi.org/10.1038/s41431-022-01242-3