Rafeeq Misbahuddin M, Murad Hussam Aly Sayed, Ullah Samee, Ahmed Zaheer, Alam Qamre, Bilal Muhammad, Habib Alaa Hamed, Sain Ziaullah M, Khan Muhammad Jawad, Umair Muhammad
Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
National Center for Bioinformatics (NCB), Quaid-i-Azam University, Islamabad, Pakistan.
Front Genet. 2023 Jan 17;13:1117500. doi: 10.3389/fgene.2022.1117500. eCollection 2022.
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. 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. 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). This study has not only expanded the mutation spectrum in the gene but also facilitated the diagnosis and genetic counseling of related features in affected families.
T-box家族成员是一类转录因子，其特征在于与称为T-box的DNA结合结构域相对应的高度保守残基。TBX2参与了多个发育过程，如协调多种组织和器官（包括肺、四肢、心脏、肾脏、颅面结构和乳腺）的细胞命运、模式形成和形态发生。在本研究中，我们对一名表现出严重软骨发育不全并伴有发育迟缓的先证者进行了临床和遗传学特征分析。本研究进行了全外显子组测序（WES）、桑格测序和三维蛋白质建模。全外显子组测序在TBX2中发现了一个新的无义变异（c.529A>T；p.Lys177*；NM_005994.4）。三维TBX2蛋白质建模显示突变蛋白大幅减少，这可能导致功能丧失（LOF）或无义介导的衰变（NMD）。本研究不仅扩展了该基因的突变谱，还为受影响家庭中相关特征的诊断和遗传咨询提供了便利。
