PDF(Pubmed)
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.
摘要：
背景：T-box家族成员是转录因子，其特征是与称为T-box的DNA结合域相对应的高度保守的残基。TBX2参与了几个发育过程，比如协调细胞命运，图案化,以及各种组织和器官的形态发生，包括肺,四肢,心,肾脏，颅面结构,还有乳腺.方法：在本研究中，我们已经在临床和遗传学上对一个先证者进行了表征，该先证者显示出严重的软骨发育不良伴发育迟缓。全外显子组测序(WES),桑格测序,在本研究中进行了3D蛋白质建模。结果:全外显子组测序揭示了TBX2中的新的无义变体(c.529A>T;p.Lys177*;NM_005994.4)。3D-TBX2蛋白建模显示突变蛋白的大量减少，这可能导致功能丧失(LOF)或无义介导的衰变(NMD)。结论：本研究不仅扩大了TBX2基因的突变谱，而且有助于对患病家庭相关特征的诊断和遗传咨询。
