Different optineurin mutation pattern in primary open-angle glaucoma
Different optineurin mutation pattern in primary open-angle glaucoma
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DOI：
10.1167/iovs.02-0693
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Pang, CP
中科院分区：
文献类型：
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作者：
Leung, YF;Fan, BJ;Pang, CP
目的.视神经磷酸酶基因（OPTN）是除MYOC以外的第二个已被鉴定为与原发性开角型青光眼（POAG）相关的基因。本研究对中国人原发性开角型青光眼患者OPTN基因的序列改变进行了研究。通过聚合酶链反应-构象敏感凝胶电泳和DNA测序，对119例散发性POAG患者和126例无关对照者的OPTN所有编码外显子（包括内含子-外显子边界）进行了序列改变筛查。确定了16个序列变化：3例已报告（T34 T、M98 K和R545 Q），13例为新报告（T49 T、E103 D、V148 V、P199 P、T202 T、H486 R、IVS 6 - 5 T-->C、IVS 610 G-->A、IVS 7 + 24 G-->A、IVS 8 + 20 G-->A、IVS 13 + 21 C-->G、IVS 15 + 10 G-->A和IVS 15 - 48 C-->A）。其中E103 D、H486 R、V148 V和IVS 13 + 21 C-->G仅见于POAG患者，而P199 P、T202 T和IVS 8 + 20 G-->A仅见于对照组。IVS 7 + 24 G-->A基因型与原发性开角型青光眼有显著相关性（P = 0.02，Fisher双尾精确检验），并与杯盘比增加有显著相关性（P = 0.005，Mann-Whitney检验）。本研究的发现丰富了OPTN基因作为POAG致病基因的证据，并提示中国人OPTN基因突变模式与白人不同。在这项研究中检测到的广泛的推定突变表明，OPTN的结构和功能破坏可能有助于青光眼的发病机制。
PURPOSE. The optineurin gene (OPTN) is the second gene besides MYOC in which mutations have been identified to be associated with primary open-angle glaucoma (POAG). In this study, sequence alterations in the OPTN gene associated with POAG in Chinese subjects were investigated.METHODS. All the coding exons of OPTN were screened, including the intron-exon boundaries, for sequence alterations in a Chinese sample of 119 sporadic patients with POAG and 126 unrelated control subjects by polymerase chain reaction- conformation-sensitive gel electrophoresis and DNA sequencing.RESULTS. Sixteen sequence changes were identified: 3 had been reported (T34T, M98K, and R545Q) and 13 were novel (T49T, E103D, V148V, P199P, T202T, H486R, IVS6-5T-->C, IVS610G-->A, IVS7+24G-->A, IVS8+20G-->A, IVS13+21C-->G, IVS15+10G-->A, and IVS15-48C-->A). Among them, only E103D, H486R, V148V, and IVS13+21C-->G were found exclusively in patients with POAG, whereas P199P, T202T, and IVS8+20G-->A were present only in control subjects. The genotype of IVS7+24G-->A showed a significant association with POAG (P = 0.02, Fisher two-tailed exact test) and with and increased cup-to-disc ratio in these patients (P = 0.005, Mann-Whitney test).CONCLUSIONS. The findings in the current study enrich the evidence on the OPTN gene as a causative gene for POAG and suggest a different mutation pattern of OPTN in Chinese than in whites. The wide spectrum of putative mutations detected in this study suggests that both structural and functional disruptions in OPTN may contribute to the pathogenesis of glaucoma.