Novel myocilin mutation in a Chinese family with juvenile-onset open-angle glaucoma
Novel myocilin mutation in a Chinese family with juvenile-onset open-angle glaucoma
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DOI：
10.1001/archopht.124.1.102
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
Pang, CP
中科院分区：
文献类型：
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作者：
Fan, BJ;Leung, DYL;Pang, CP
目的：目的探讨一个中国人青少年型开角型青光眼（juvenile-onset open-angle glaucoma，JOAG）家系的遗传学病因。在一个三代青光眼家系中，我们对6名成员进行了肌球蛋白（myocilin，MYOC）和视神经磷酸酶（optineurin，OPTN）的突变筛查和载脂蛋白E（apolipoprotein E，APOE）多态性研究，其中2名为JOAG患者，2名为高眼压患者，2例无症状。正常对照组包括200名无关的中国受试者。用编码野生型或突变MYOC互补DNA的表达载体转染COS-7细胞系。结果：发现一个错义MYOC突变734 G> A：Cys 245 Tyr。该家族4名成员均患有JOAG或高眼压症，但无症状的家族成员均未发生。未观察到OPTN变化。APOE多态性频率与对照组相似。Cys 245 Tyr MYOC突变与家族内的疾病共分离。Cys 245 Tyr突变MYOC蛋白形成同源多聚体复合物，其以大于其野生型对应物的分子量迁移。结论：Cys 245 Tyr MYOC启动是该家系JOAG的遗传原因。这种突变可能是在MYOC半胱氨酸之间形成共价键后发生的.临床相关性：基因检测. MYOC突变的检测可能有助于预测JOAG家族中新发病例。
Objective: To search for the genetic cause of juvenile-onset open-angle glaucoma (JOAG) in a Chinese family.Methods: In a 3-generation glaucoma family affected with JOAG or ocular hypertension, we screened myocilin (MYOC) and optineurin (OPTN) for mutations and investigated apolipoprotein E (APOE) polymorphisms in 6 family members, 2 of them patients with JOAG, 2 patients with ocular hypertension, and 2 patients who were asymptomatic. Normal controls included 200 unrelated Chinese subjects. The COS-7 cell line was transfected with expression vectors encoding wild-type or mutated MYOC complementary DNA. Cellular and secreted MYOC proteins were characterized by Western blotting.Results: One missense MYOC mutation, 734G > A: Cys245Tyr, was identified. It occurred in all 4 family members afflicted with JOAG or ocular hypertension but not in asymptomatic family members. No OPTN variations were observed. APOE polymorphism frequencies were similar to those for controls. The Cys245Tyr MYOC mutation cosegregated with the disorder within (lie family. It was absent in the 200 control subjects, The Cys245Tyr mutant MYOC protein formed homomultimeric complexes that migrated at Molecular weights larger than their wild-type counterparts. These mutant complexes remained sequestered intracellularly in COS-7 cells.Conclusions: The Cys245Tyr MYOC Initiation was the genetic cause of JOAG in this Chinese family. This mutation may after covalent bonds that formed between MYOC cysteines.Clinical Relevance: Genetic tests. of MYOC mutations may be beneficial to predict new cases of the disease in families with JOAG.