Distribution of Optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States
Distribution of Optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States
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DOI：
10.1097/01.ijg.0000212255.17950.42
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发表时间：
2006-10-01
影响因子：
2
通讯作者：
Wiggs, Janey L.
中科院分区：
文献类型：
--
作者：
Hauser, Michael A.;Sena, Dayse Figueiredo;Wiggs, Janey L.
目的：先前的研究表明，视神经磷酸酶（OPTN）序列变异有助于种族同质人群中的低眼压性青光眼（LTG）。本研究的目的是评估OPTN序列变异体在来自美国的种族多样性LTG患者人群中的患病率，并描述在LTG患者中优先发现的OPTN序列变异体患者的表型。使用高通量测序技术，对从67名LTG患者纯化的基因组DNA中筛选位于OPTN基因外显子和侧翼内含子中的DNA序列变体。高效液相色谱分析和直接基因组DNA测序。86原发性开角型青光眼先证者和100名对照patients.Results：9 OPTN DNA序列变异被确定在这个患者人群中，包括2个先前确定的杂合非同义单核苷酸多态性外显子4和5。4例LTG患者严重的疾病和积极的青光眼家族史，被发现有DNA序列的变化没有发现在原发性开角型青光眼先证者或控制individualincluding the previousreported E50K variation.Conclusions：这项研究的结果支持罕见的OPTN序列变异与家族形式的LTG的关联。E50K突变似乎与LTG的严重形式有关，虽然罕见，但在有风险的患者中鉴定这种序列变异可能有助于指导适当的治疗。
Purpose: Previous studies have suggested that Optineurin (OPTN) sequence variants contribute to low-tension glaucoma (LTG) in ethnically homogeneous populations. The purpose of this study is to evaluate the prevalence of OPTN sequence variants in an ethnically diverse population of LTG patients from the United States, and to describe the phenotype of patients with OPTN sequence variants preferentially found in LTG patients.Methods: Genomic DNA purified from 67 LTG patients was screened for DNA sequence variants located in the exons and flanking introns of the OPTN gene using high-performance liquid chromatography analysis and direct genomic DNA sequencing. Eighty-six primary open-angle glaucoma probands and 100 control patients were also analyzed.Results: Nine OPTN DNA sequence variants were identified in this patient population including the 2 previously identified heterozygous nonsynonymous single-nucleotide polymorphisms in exons 4 and 5. Four LTG patients with severe disease and positive family history of glaucoma, were found to have DNA sequence changes not found in primary open-angle glaucoma probands or control individuals including the previously reported E50K variation.Conclusions: The results of this study support the rare association of OPTN sequence variants with familial forms of LTG. The E50K mutation seems to be associated with a severe form of LTG, and although rare, the identification of this sequence variant in patients at risk may help direct appropriate therapy.