Decreased Plasma COMP and Increased Plasma CTX-II Levels in a Chinese Pseudoachondroplasia Family with Novel COMP Mutation.
Decreased Plasma COMP and Increased Plasma CTX-II Levels in a Chinese Pseudoachondroplasia Family with Novel COMP Mutation.
复制标题
具有新型 COMP 突变的中国假性软骨发育不全家族中血浆 COMP 降低和血浆 CTX-II 水平升高
DOI：
10.1155/2017/5809787
复制
发表时间：
2017
影响因子：
--
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Gu C;Yang Z;Tan H;Zhang Y;Lu Y;Ma Y
假性软骨发育不全（PSACH）是一种常染色体显性骨软骨发育不良，由编码软骨寡聚基质蛋白（COMP）的基因突变引起。PSACH的准确临床诊断有时很困难。我们在一个中国PRACH家系中发现了一个新的COMP突变（c.1675G>A，p.Glu559Lys）。检测4例患者血浆COMP和II型胶原（CTX-II）水平。结果显示，3例COMP基因突变的PACH患者血浆COMP水平显著降低，而血浆CTX-Ⅱ水平显著升高。但症状前携带者与年龄匹配者血浆COMP和CTX-Ⅱ水平无显著性差异。体外分析和免疫荧光显示野生型COMP在细胞质中均匀表达，但突变蛋白在HEK-293细胞内不规则地积累。Western blot结果显示，转染12 h和24 h后，突变型COMP在细胞中的表达量明显高于野生型COMP。三维结构分析表明，突变体COMP的二级结构发生了3个变化，推测COMP的新突变可能导致突变蛋白在细胞内积累。降低血浆COMP和增加血浆CTX-II可能作为PSACH的诊断标志物，但可能不适用于前驱载体。
Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Accurate clinical diagnosis of PSACH is sometimes difficult. Here, we identified a novel COMP mutation (c.1675G>A, p.Glu559Lys) in a Chinese PSACH family. We detected the plasma levels of COMP and type II collagen (CTX-II) in the four affected individuals. The results showed the levels of plasma COMP significantly decreased and plasma CTX-II significantly increased in the three PSACH patients with COMP mutation. However, both plasma levels of COMP and CTX-II were not to have found significant difference between the presymptomatic carrier and the age-matched subjects. In vitro analysis and immunofluorescence displayed wild type COMP homogenously expressed in cytoplasm, but mutant proteins were irregularly accumulated inside the HEK-293 cells. Western blot revealed that the quantity of the mutant COMP was more compared to wild type COMP in cells after transfection for 12 hours and 24 hours. Subsequently, 3D structural analysis showed three changes have taken place in secondary structure of the mutant COMP. In conclusion, the novel mutation of COMP may result in intracellular accumulation of the mutant protein. Decreased plasma COMP and increased plasma CTX-II may potentially serve as diagnostic markers of PSACH but may not be applicable in the presymptomatic carrier.
登录
查看更多内容
DOI：
10.1038/ejhg.2014.30
发表时间：
2014-11
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.9
作者：
Hecht, JT;Hayes, E;Duke, PJ
通讯作者：
Duke, PJ
影响因子：
6.9
作者：
Schmitz, Markus;Niehoff, Anja;Zaucke, Frank
通讯作者：
Zaucke, Frank
影响因子：
4.1
作者：
Tan, Kemin;Lawler, Jack
通讯作者：
Lawler, Jack
影响因子：
5.8
作者：
Arnold, K;Bordoli, L;Schwede, T
通讯作者：
Schwede, T