Gong Gordon, Kosoko-Lasaki Omofolasade, Haynatzki Gleb R, Wilson M Roy
Osteoporosis Research Center, Creighton University Omaha, NE 68131, USA.
Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R91-102. doi: 10.1093/hmg/ddh074. Epub 2004 Feb 5.
Primary open-angle glaucoma (POAG) is a complex disease with unknown causes. However, in the past decade, POAG has been linked to six chromosomal regions, of which the gene MYOC encoding myocilin and the gene OPTN encoding optineurin have been identified to harbor causal mutations (disease-causing variants, DCV). POAG caused by DCV at MYOC has been termed "myocilin glaucoma". Clinically, DCV at MYOC may manifest as a typical POAG, normal tension glaucoma, or ocular hypertension without glaucoma. Individuals with the Arg46Stop mutation that almost knocks out the entire coding sequence may have severe glaucoma or no glaucoma. Genetically, myocilin glaucoma follows autosomal dominant, recessive or no pattern of inheritance. DCV at MYOC cause POAG in interaction with environmental factors and DCV at other loci. Most DCV at MYOC are relatively young, and the Gln368Stop mutation is exclusively European in origin. The overall frequency of DCV at MYOC is similar among African, Caucasian and Asian probands with POAG. Because of this fact and the higher prevalence of POAG in African descendants compared with Caucasians or Asians, the overall frequency of DCV at MYOC is several-fold higher in the general population of African descendants, which is in part responsible for their higher prevalence of POAG. Although the Arg46Stop mutation was often observed in normal controls, Arg46Stop carriers tend to have higher risk of developing POAG. Polymorphisms at several loci including MYOC are associated with POAG, and play an important role in the pathogenesis of POAG.
原发性开角型青光眼（POAG）是一种病因不明的复杂疾病。然而，在过去十年中，POAG已与六个染色体区域相关联，其中已确定编码肌纤蛋白的基因MYOC和编码视紫质神经元的基因OPTN含有致病变异（致病变体，DCV）。由MYOC处的DCV引起的POAG被称为“肌纤蛋白性青光眼”。临床上，MYOC处的DCV可能表现为典型的POAG、正常眼压性青光眼或无青光眼的高眼压症。具有几乎敲除整个编码序列的Arg46Stop突变的个体可能患有严重青光眼或无青光眼。在遗传方面，肌纤蛋白性青光眼遵循常染色体显性、隐性或无遗传模式。MYOC处的DCV与环境因素和其他基因座处的DCV相互作用导致POAG。MYOC处的大多数DCV相对年轻，并且Gln368Stop突变仅起源于欧洲。在患有POAG的非洲、白种人和亚洲先证者中，MYOC处DCV的总体频率相似。由于这一事实以及与白种人或亚洲人相比非洲后裔中POAG的患病率更高，MYOC处DCV在非洲后裔普通人群中的总体频率高出几倍，这部分解释了他们中POAG患病率较高的原因。尽管在正常对照中经常观察到Arg46Stop突变，但Arg46Stop携带者患POAG的风险往往更高。包括MYOC在内的几个基因座的多态性与POAG相关，并在POAG的发病机制中起重要作用。
