Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta.
Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta.
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证实与成骨不全相关的 COL1A2 基因 p.G337C 突变的致病性
DOI：
10.1097/md.0000000000007783
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发表时间：
2017-09
期刊：
影响因子：
1.6
通讯作者：
Yan F
中科院分区：
文献类型：
--
作者：
Jia M;Shi R;Zhao X;Fu Z;Bai Z;Sun T;Zhao X;Wang W;Xu C;Yan F
作为金标准的突变分析在成骨不全（OI）的诊断中特别重要，并且在早期诊断时可以预防。在这项研究中，我们的目的是分析的临床和遗传资料的OI家系，以及确认的有害性质的突变。确定了一个OI家系。所有家庭成员都接受了仔细的临床检查，并抽取了血液进行遗传分析。筛选与OI有关的基因的突变。利用生物信息学分析预测了突变蛋白的功能和结构。先证者是一个9个月大的胎儿，显示异常的超声图像。出生时发现面部短而三角形，巩膜呈蓝色。她几乎不能走路，直到2岁才遭受多处骨折。母亲身材矮小，多发骨折，巩膜青紫，四肢畸形。在其母亲和她的COL1A2基因中发现了一个杂合错义突变c.1009G>T（p.G337C），生物信息学分析表明p.G337在多个物种中高度保守，该突变可能改变了胶原蛋白的结构和功能。我们认为COL1A2基因中的突变p.G337C通过影响胶原蛋白的结构和功能而致病。
Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen.