A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia
Misbahuddin M Rafeeq, Hussam Aly Sayed Murad, Samee Ullah, Zaheer Ahmed, Qamre Alam, Muhammad Bilal, Alaa Hamed Habib, Ziaullah M Sain, Muhammad Jawad Khan, Muhammad Umair,
Frontiers in Genetics (2022)
DOI: https://doi.org/10.3389/fgene.2022.1117500
Abstract
Background T-box family members are transcription factors characterized by highly conserved residues corresponding to the DNA-binding domain known as the T-box. TBX2 has been implicated in several developmental processes, such as coordinating cell fate, patterning, and morphogenesis of a wide range of tissues and organs, including lungs, limbs, heart, kidneys, craniofacial structures, and mammary glands.
Methods In the present study, we have clinically and genetically characterized a proband showing a severe form of chondrodysplasia with developmental delay. Whole-exome sequencing (WES), Sanger sequencing, and 3D protein modeling were performed in the present investigation.
Results Whole-exome sequencing revealed a novel nonsense variant (c.529A>T; p.Lys177*; NM_005994.4) in TBX2. 3D-TBX2 protein modeling revealed a substantial reduction of the mutated protein, which might lead to a loss of function (LOF) or nonsense-mediated decay (NMD).
Conclusion This study has not only expanded the mutation spectrum in the gene TBX2 but also facilitated the diagnosis and genetic counseling of related features in affected families.
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Citation
@article{ullah2022,
author = {Ullah, Samee},
title = {A Novel de Novo Loss of Function Variant in the {DNA-binding}
Domain of {TBX2} Causes Severe Osteochondrodysplasia},
volume = {13},
number = {1117500},
date = {2022-03-01},
url = {https://www.frontiersin.org/articles/10.3389/fgene.2022.1117500/full},
doi = {10.3389/fgene.2022.1117500},
langid = {en}
}