AUTHOR=Rafeeq Misbahuddin M. , Murad Hussam Aly Sayed , Najumuddin  , Ullah Samee , Ahmed Zaheer , Alam Qamre , Bilal Muhammad , Habib Alaa Hamed , Sain Ziaullah M. , Khan Muhammad Jawad , Umair Muhammad 

TITLE=Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1117500

DOI=10.3389/fgene.2022.1117500

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Whole-exome sequencing revealed a novel nonsense variant (c.529A&gt;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).</p><p><bold>Conclusion:</bold> This study has not only expanded the mutation spectrum in the gene <italic>TBX2</italic> but also facilitated the diagnosis and genetic counseling of related features in affected families.</p>