Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
Ophthalmology. 2013 Jun;120(6):1135-43. doi: 10.1016/j.ophtha.2012.11.029. Epub 2013 Feb 28.
To determine the proportion of all Myocilin coding mutations responsible for advanced primary open-angle glaucoma (POAG) in early-age-at-onset individuals and to investigate the prevalence of exon 3 Myocilin mutations in advanced POAG at any age at onset in a large Australasian cohort.
Cross-sectional study using a national disease registry.
One thousand sixty individuals with advanced POAG (103 with age at onset of 40 years or younger) and 320 with nonadvanced POAG all recruited by the Australian and New Zealand Registry of Advanced Glaucoma.
Participants were examined and referred by their eye practitioner, and Myocilin genetic testing was performed by direct sequencing. Cascade genetic testing was made available for relatives of participants found to carry a Myocilin mutation.
Advanced glaucoma diagnosis based on strict visual field entry criteria. Prevalence and spectrum of Myocilin mutations in individuals with advanced and nonadvanced POAG.
This is the first study to report Myocilin mutations in an advanced POAG cohort. No pathogenic Myocilin mutations were identified in exons 1 and 2 in early-age-at-onset advanced POAG cases. Exon 3 Myocilin mutations were identified in 45 advanced POAG patients (4.2%), which is significantly higher (P = 0.02) compared with nonadvanced POAG patients (1.6%). A novel mutation (Trp373X) and a new variant of uncertain pathogenicity (Ala447Thr) also were reported. The prevalence of Myocilin mutations rose from 16% to 40% in selected advanced POAG subgroups based on different thresholds of maximum recorded intraocular pressure, age at diagnosis, and the presence and strength of positive family history. Twenty-six individuals with Myocilin mutations were identified through cascade genetic testing of first-degree relatives of affected mutation carriers.
The prevalence of Myocilin mutations in glaucoma cases with severe visual field loss is significantly greater than in nonadvanced glaucoma patients. Myocilin screening in phenotypically selected cases can have a much higher yield than in previous unselected series. Identifying individuals who have Myocilin mutations provides an opportunity to screen at-risk clinically unaffected relatives and to reduce glaucoma blindness through early management and intervention.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
确定所有导致早发性原发性开角型青光眼（POAG）的 Myocilin 编码突变在发病年龄较早的个体中的比例，并在一个大型澳大拉西亚队列中调查任何发病年龄的晚期 POAG 中 exon 3 Myocilin 突变的患病率。
使用全国疾病登记处进行的横断面研究。
1060 名患有晚期 POAG（103 名发病年龄在 40 岁或以下）和 320 名非晚期 POAG 的个体，均由澳大利亚和新西兰高级青光眼登记处招募。
参与者由他们的眼科医生检查和转诊，通过直接测序进行 Myocilin 基因检测。对发现携带 Myocilin 突变的参与者的亲属进行级联基因检测。
根据严格的视野进入标准诊断为晚期青光眼。晚期和非晚期 POAG 个体中 Myocilin 突变的患病率和谱。
这是第一项在晚期 POAG 队列中报告 Myocilin 突变的研究。在早发性晚期 POAG 病例中，未在 exon 1 和 2 中发现致病性 Myocilin 突变。在 45 名晚期 POAG 患者（4.2%）中发现了 exon 3 Myocilin 突变，这明显高于非晚期 POAG 患者（1.6%）（P = 0.02）。还报道了一种新的突变（Trp373X）和一种新的致病性不确定的变异体（Ala447Thr）。基于不同的最大记录眼内压、诊断年龄、阳性家族史的存在和强度阈值，在选定的晚期 POAG 亚组中，Myocilin 突变的患病率从 16%上升到 40%。通过对受影响突变携带者一级亲属进行级联基因检测，鉴定出 26 名 Myocilin 突变个体。
在视野严重丧失的青光眼病例中，Myocilin 突变的患病率明显高于非晚期青光眼患者。在表型选择的病例中进行 Myocilin 筛查，其产量可能远高于以前未选择的系列。鉴定出具有 Myocilin 突变的个体为筛查有风险但未受影响的临床亲属提供了机会，并通过早期管理和干预降低青光眼致盲率。
作者没有与本文讨论的任何材料有关的专有或商业利益。
