• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss
【2h】

Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss

机译：CYP1B1基因突变在青少年开角型青光眼中的发生

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Importance: Juvenile open-angle glaucoma (JOAG) is a severe neurodegenerative eye disorder in which most of the genetic contribution remains unexplained. Objective: To assess the prevalence of pathogenic CYP1B1 sequence variants in an Australian cohort of patients with JOAG and severe visual field loss. Design, setting, and participants: For this cohort study, we recruited 160 patients with JOAG classified as advanced (n = 118) and nonadvanced (n = 42) through the Australian and New Zealand Registry of Advanced Glaucoma from January 1, 2007, through April 1, 2014. Eighty individuals with no evidence of glaucoma served as a control group. We defined JOAG as diagnosis before age 40 years and advanced JOAG as visual field loss in 2 of the 4 central fixation squares on a reliable visual field test result. We performed direct sequencing of the entire coding region of CYP1B1. Data analysis was performed in October 2014. Main outcomes and measures: Identification and characterization of CYP1B1 sequence variants. Results: We identified 7 different pathogenic variants among 8 of 118 patients with advanced JOAG (6.8%) but none among the patients with nonadvanced JOAG. Three patients were homozygous or compound heterozygous for CYP1B1 pathogenic variants, which provided a likely basis for their disease. Five patients were heterozygous. The allele frequency among the patients with advanced JOAG (11 in 236 [4.7%]) was higher than among our controls (1 in 160 [0.6%]; P = .02; odds ratio, 7.8 [95% CI, 0.02-1.0]) or among the control population from the Exome Aggregation Consortium database (2946 of 122 960 [2.4%]; P = .02; odds ratio, 2.0 [95% CI, 0.3-0.9]). Individuals with CYP1B1 pathogenic variants, whether heterozygous or homozygous, had worse mean (SD) deviation on visual fields (-24.5 [5.1] [95% CI, -31.8 to -17.2] vs -15.6 [10.0] [95% CI, -17.1 to -13.6] dB; F1,126 = 5.90; P = .02; partial ηp2 = 0.05) and were younger at diagnosis (mean [SD] age, 23.1 [8.4] [95% CI, 17.2-29.1] vs 31.5 [8.0] [95% CI, 30.1-33.0] years; F1,122 = 7.18; P = .008; ηp2 = 0.06) than patients without CYP1B1 pathogenic variants. Conclusions and relevance: Patients with advanced JOAG based on visual field loss had enrichment of CYP1B1 pathogenic variants and a more severe phenotype compared with unaffected controls and patients with nonadvanced JOAG.
机译：重要性：少年开角型青光眼（JOAG）是一种严重的神经退行性眼部疾病，其中大部分遗传贡献仍无法解释。目的：评估澳大利亚人群JOAG和严重视野丧失患者中病原性CYP1B1序列变异的发生率。设计，背景和参加者：对于本队列研究，我们从2007年1月1日开始，通过澳大利亚和新西兰的高级青光眼注册中心招募了160例分类为晚期（n = 118）和非晚期（n = 42）的JOAG患者。 2014年4月1日。80名无青光眼证据的人作为对照组。根据可靠的视野测试结果，我们将JOAG定义为40岁之前的诊断，而将JOAG定义为4个中央固定方格中2个的视野丧失。我们对CYP1B1的整个编码区进行了直接测序。在2014年10月进行了数据分析。主要结果和措施：CYP1B1序列变异的鉴定和表征。结果：我们在118例晚期JOAG患者中有8例（6.8％）中发现了7种不同的致病变异，而在非晚期JOAG患者中没有发现。 3例患者的CYP1B1致病变异为纯合子或复合杂合子，为他们的疾病提供了可能的基础。 5例为杂合子。晚期JOAG患者的等位基因频率（236例中的11例[4.7％]）高于对照组（160例中的1例[0.6％]； P = .02；比值比为7.8 [95％CI，0.02-1.0] ]）或来自Exome Aggregation Consortium数据库的对照人群中（122946中的2946 [2.4％]； P; = .02；优势比为2.0 [95％CI，0.3-0.9]）。具有CYP1B1致病性变体的个体，无论是杂合的还是纯合的，在视野上的平均（SD）偏差都更差（-24.5 [5.1] [95％CI，-31.8至-17.2]与-15.6 [10.0] [95％CI，- 17.1至-13.6] dB； F1,126 = 5.90； P = .02；部分ηp2= 0.05），并且在诊断时更年轻（平均[SD]年龄，23.1 [8.4] [95％CI，17.2-29.1] vs 31.5） [8.0] [95％CI，30.1-33.0]年； F1,122 = 7.18； P = .008；ηp2= 0.06）比没有CYP1B1致病变异的患者高。结论和相关性：与未受影响的对照组和非晚期JOAG患者相比，患有因视野丧失而导致的晚期JOAG患者的CYP1B1致病性变异丰富，且表型更为严重。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号