Author Correction: Mutations in COMP cause familial carpal tunnel syndrome.
Author Correction: Mutations in COMP cause familial carpal tunnel syndrome.
复制标题
作者更正：COMP 突变导致家族性腕管综合征。
DOI：
10.1038/s41467-020-17845-7
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发表时间：
2020
影响因子：
16.6
通讯作者：
Gao,Bo
中科院分区：
文献类型：
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作者：
Li,Chunyu;Wang,Ni;Schäffer,AlejandroA;Liu,Xilin;Zhao,Zhuo;Elliott,Gene;Garrett,Lisa;Choi,NgaTing;Wang,Yueshu;Wang,Yufa;Wang,Cheng;Wang,Jin;Chan,Danny;Su,Peiqiang;Cui,Shusen;Yang,Yingzi;Gao,Bo
腕管综合征（CTS）是最常见的周围神经卡压综合征，影响很大一部分普通人群。 CTS 与遗传易感性有关，但致病基因仍然难以捉摸。在这里，我们报告了在患有或不患有多发性骨骺发育不良（MED）的两个大家族中鉴定出软骨寡聚基质蛋白（COMP）中的两个突变，这些突变与 CTS 分离。这两种突变都会损害肌腱细胞对 COMP 的分泌，但与 MED 相关的突变也会扰乱软骨细胞中 COMP 的分泌。 CTS 特异性突变的进一步功能表征揭示了患者活检和小鼠模型中肌腱/韧带相似的组织学和分子变化。突变型 COMP 无法正常寡聚并被困在 ER 中，导致 ER 应激诱导的未折叠蛋白反应和细胞死亡，从而导致肌腱/韧带炎症、进行性纤维化和细胞组成变化。细胞外基质（ECM）组织也发生改变。我们的研究揭示了 CTS 发病机制中以前未被认识的机制。
Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, affecting a large proportion of the general population. Genetic susceptibility has been implicated in CTS, but the causative genes remain elusive. Here, we report the identification of two mutations in cartilage oligomeric matrix protein (COMP) that segregate with CTS in two large families with or without multiple epiphyseal dysplasia (MED). Both mutations impair the secretion of COMP by tenocytes, but the mutation associated with MED also perturbs its secretion in chondrocytes. Further functional characterization of the CTS-specific mutation reveals similar histological and molecular changes of tendons/ligaments in patients’ biopsies and the mouse models. The mutant COMP fails to oligomerize properly and is trapped in the ER, resulting in ER stress-induced unfolded protein response and cell death, leading to inflammation, progressive fibrosis and cell composition change in tendons/ligaments. The extracellular matrix (ECM) organization is also altered. Our studies uncover a previously unrecognized mechanism in CTS pathogenesis.