Wang Dan Yi, Fan Bao Jian, Canlas Oscar, Tam Pancy O S, Ritch Robert, Lam Dennis S C, Fan Dorothy S P, Pang Chi Pui
Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Mol Vis. 2004 Nov 9;10:851-6.
To analyze the role of the two primary open angle glaucoma (POAG) genes, myocilin (MYOC) and optineurin (OPTN), in a large Philippine family segregating autosomal dominant juvenile onset open angle glaucoma (JOAG).
The coding sequences of the MYOC and OPTN genes were screened in 27 family members by polymerase chain reaction and direct sequencing. The specific MYOC promoter polymorphism (MYOC.mtl) was identified by restriction endonuclease assay. All of the ABI MD-10 microsatellite markers on chromosomes 1, 2, 3, 7, 8, and 10, which harbor the six known POAG loci, were analyzed for linkage with POAG.
No mutation was identified in this large kindred. Instead, three polymorphisms (-80G->A, -1000G->C, R76K) in MYOC and four polymorphisms (T34T, M98K, R545Q, IVS7+24G->A) in OPTN were found. All markers flanking the six known POAG loci gave LOD scores not more than 1.1. Non-parametric linkage analysis for all these markers resulted in p values more than 0.05.
Both mutation testing and linkage analysis provide strong evidence against MYOC and OPTN being the causative gene in this large family. It indicates that unidentified genes will underlie the occurrence of glaucoma in this family.
分析两个原发性开角型青光眼（POAG）基因，即肌纤蛋白（MYOC）和视紫质神经元（OPTN），在一个菲律宾大家族中常染色体显性遗传青少年型开角型青光眼（JOAG）遗传中的作用。
采用聚合酶链反应和直接测序法对27名家族成员的MYOC和OPTN基因编码序列进行筛查。通过限制性内切酶分析鉴定特定的MYOC启动子多态性（MYOC.mtl）。对1、2、3、7、8和10号染色体上所有携带六个已知POAG基因座的ABI MD - 10微卫星标记进行与POAG的连锁分析。
在这个大家族中未发现突变。相反，在MYOC中发现了三个多态性位点（-80G→A、-1000G→C、R76K），在OPTN中发现了四个多态性位点（T34T、M98K、R545Q、IVS7 + 24G→A）。六个已知POAG基因座两侧的所有标记的对数优势分数均不超过1.1。对所有这些标记进行非参数连锁分析，得到的p值均大于0.05。
突变检测和连锁分析均提供了有力证据，表明MYOC和OPTN不是这个大家族中青光眼致病基因。这表明该家族青光眼的发生存在未明确的基因。
