背景:胶原蛋白,最丰富的人类蛋白质,是组织和器官如皮肤中的细胞外基质(ECM)的重要组成部分,骨头,韧带,和肌腱。胶原蛋白分泌是一个复杂的,涉及许多分子的多阶段过程。在该过程中发挥主要功能之一的蛋白质是由MIA3基因编码的TANGO1。在Ehlers-Danlos综合征(hEDS)的高移动型中,最常见的胶原病之一,没有已知的遗传背景,观察到许多分子(包括胶原蛋白)的分泌中断。
目的:本研究的目的是评估MIA3基因在hEDS患者中的作用。
方法:100名临床诊断为hEDS且下一代测序(NGS)检测阴性的结缔组织疾病患者(例如Ehlers-Danlos综合征,成骨不完全(OI),马凡氏综合征,和其他)进行了MIA3基因的分子变化测试。
结果:在100名受检患者中,在MIA3基因中检测到14个单一的构造变更。十三是错义良性或可能良性,而1个变体(c.567dup,p.Leu1880ThrfsTer6)截短了TANGO1蛋白。
结论:我们假设MIA3基因中截断变体(c.5637dup)的存在和结缔组织蛋白分泌的中断可能是测试患者临床症状的致病机制之一,但是这些发现需要更全面的多维调查。
BACKGROUND: Collagen, the most abundant human protein, is a significant component of the extracellular matrix (ECM) in tissues and organs like skin, bone, ligaments, and tendons. Collagen secretion is a complex, multistage process involving many molecules. A protein playing one of the main functions in this process is
TANGO1 encoded by MIA3 gene. In the hypermobile type of Ehlers-Danlos syndrome (hEDS), one of the most common collagenopathies with no known genetic background, disrupted secretion of many molecules (including collagen) was observed.
OBJECTIVE: The aim of this study was the evaluation of the MIA3 gene role in hEDS patients.
METHODS: One hundred patients with clinically diagnosed hEDS and negative next-generation sequencing (NGS) testing for connective tissue disorder (e.g. Ehlers-Danlos syndrome, osteogenesis imperfect (OI), Marfan syndrome, and others) were tested for molecular changes in the MIA3 gene.
RESULTS: Among the 100 tested patients, 14 single structural changes in the MIA3 gene were detected. Thirteen were missense benign or likely benign, while 1 variant (c.567dup, p.Leu1880ThrfsTer6) was truncating the
TANGO1 protein.
CONCLUSIONS: We suppose that the presence of truncating variant (c.5637dup) in the MIA3 gene and disrupted secretion of connective tissue protein may be one of the pathogenic mechanisms of clinical symptoms present in the tested patient, but these findings require a more comprehensive multidimensional investigation.