Zhuo Ye-Hong, Wei Yan-Tao, Bai Yu-Jing, Duan Shan, Lin Ming-Kai, Saragovi H Uri, Ge Jian
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Mol Vis. 2008 Aug 22;14:1533-9.
Glaucoma is the leading cause of irreversible blindness worldwide. Most of the cases are primary open angle glaucoma (POAG). POAG is a genetically heterogenous disease; autosomal dominance is the most frequent type of monogenic inheritance. In this study, we identified the genotype of a MYOC mutation and investigated the phenotype of a Chinese juvenile-onset open angle glaucoma (JOAG) pedigree (GZ.1 pedigree).
Blood samples were obtained from 24 participants. We performed sequence and gene linkage analysis in the GZ.1 pedigree retrospectively. Comprehensive ophthalmologic examinations were performed for each family member. Pharmacological treatment or filtering surgery was performed as needed according to the intraocular pressure (IOP) of each individual.
A Pro370Leu myocilin mutation located in exon 3 of MYOC was identified in 24 members of the GZ.1 pedigree. Sixteen patients had juvenile-onset primary open-angle glaucoma (JOAG), and the others participating in the project had no such genotype. Analysis of polymorphic microsatellite markers indicated that the disease in GZ.1 is autosomal dominant inheritance. The patients in GZ.1 are characterized by early age of onset (before 35 years of age), severe clinical presentations, and high intraocular pressure unresponsive to pharmacological treatment; requiring 89.5% of the patients to undergo filtering surgery. Fortunately, the success rate of surgery was high. None of the patients required further medical treatment and only one demonstrated low IOP fundus changes.
This is the first evidence of a founder effect for a Pro370Leu myocilin mutation in a Chinese POAG pedigree. The family with the Pro370Leu myocilin mutation presents with juvenile-onset glaucoma. After 10 years of follow-up, it is evident that the mutation is closely associated with the phenotype of the patients. Analysis of MYOC in JOAG patients may enable the identification of at-risk individuals and help prevent disease progression toward the degeneration of the optic nerve, and may also contribute to genetic counseling.
青光眼是全球不可逆性失明的主要原因。大多数病例为原发性开角型青光眼（POAG）。POAG是一种基因异质性疾病；常染色体显性遗传是最常见的单基因遗传类型。在本研究中，我们鉴定了一个MYOC突变的基因型，并调查了一个中国青少年型开角型青光眼（JOAG）家系（GZ.1家系）的表型。
采集了24名参与者的血样。我们对GZ.1家系进行了回顾性序列和基因连锁分析。对每个家庭成员进行了全面的眼科检查。根据每个人的眼压（IOP），必要时进行药物治疗或滤过手术。
在GZ.1家系的24名成员中鉴定出位于MYOC第3外显子的Pro370Leu肌纤蛋白突变。16例患者患有青少年型原发性开角型青光眼（JOAG），参与该项目的其他患者没有这种基因型。多态性微卫星标记分析表明，GZ.1家系中的疾病为常染色体显性遗传。GZ.1家系的患者具有发病年龄早（35岁之前）、临床表现严重、眼压对药物治疗无反应的特点；89.5%的患者需要进行滤过手术。幸运的是，手术成功率很高。没有患者需要进一步的药物治疗，只有1例出现了低眼压眼底改变。
这是中国POAG家系中Pro370Leu肌纤蛋白突变存在奠基者效应的首个证据。携带Pro370Leu肌纤蛋白突变的家族表现为青少年型青光眼。经过10年的随访，很明显该突变与患者的表型密切相关。对JOAG患者进行MYOC分析可能有助于识别高危个体，有助于预防疾病向视神经萎缩发展，也可能有助于遗传咨询。
