%0 Case Reports
%T Case report: A novel de novo loss of function variant in the DNA-binding domain of TBX2 causes severe osteochondrodysplasia.
%A Rafeeq MM
%A Murad HAS
%A Najumuddin 
%A Ullah S
%A Ahmed Z
%A Alam Q
%A Bilal M
%A Habib AH
%A Sain ZM
%A Khan MJ
%A Umair M
%J Front Genet
%V 13
%N 0
%D 2022
%M 36733940
%F 4.772
%R 10.3389/fgene.2022.1117500
%X 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.