摘要/Abstract

摘要： 目的 ·研究 CITED2基因突变与内脏反位的关系。方法 ·选取 24例内脏反位的患者和 100名健康儿童对照，从外周血提取基因组 DNA，使用 PCR扩增技术和 Sanger测序技术来检测 CITED2的外显子区域；通过软件 Sift、PolyPhen-2、PROVEAN和 Mutation Taster预测突变是否存在致病性；使用 Y. Zhang实验室服务器构建蛋白质的三维结构，导入 SWISS-PdbViewer查看突变对蛋白质结构的影响。结果 ·在 1例内脏反位的患者中发现了 1个新发的杂合错义突变 c.418C>T（p.P140S），此突变在对照组中未发现。软件 SIFT和 Mutation Taster预测此突变具有致病性。 SWISS-PdbViewer显示，第 140位脯氨酸突变为丝氨酸后，第 137位天冬氨酸上的 3个氢键全部断开，第 140位丝氨酸和第 142位丙氨酸重新建立了一个异常弱氢键。结论 · CITED2基因 c.418C>T（p.P140S）突变可能影响 CITED2的生物学活性，与内脏反位的发生有关。
关键词: 内脏反位, CITED2基因, 基因突变
Abstract:
Objective · To analyze the correlation between CITED2 gene mutation and situs inversus. Methods · A total of 24 patients with situs inversus and 100 healthy controls were collected. The genomic DNA was isolated their peripheral blood. PCR and Sanger sequecing were employed to analyze the exons of CITED2. The potential effect of the mutation was characterizedthe software Sift, PolyPhen-2, PROVEAN and Mutation Taster. The Y. Zhang laboratory server was used to predict the three-dimensional structure of the protein, and the SWISS-PdbViewer was imported to see the impacts of the mutation on the protein structure. Results · A novel heterozygous CITED2 mutation c.418C>T (p.P140S) was identified in 1 patient with situs inversus, which was absent in all controls. The novel heterozygous p.P140S mutation was predicted to be pathogenicSIFT and Mutation Taster. The SWISS-PdbViewer showed that the mutation p.P140S caused all three hydrogen bonds on the aspartic acid at position 137 to be disconnected, and an abnormal weak hydrogen bond was re-established between the serine at position 140 and the alanine at position 142. Conclusion · The novel heterozygous mutation c.418C>T (p.P140S) may affect the biological activity of CITED2 and may be related to situs inversus.
Key words: situs inversus, CITED2 gene, gene mutation


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