Gillies Lecture: Dissecting glaucoma: understanding the molecular risk factors
Gillies Lecture: Dissecting glaucoma: understanding the molecular risk factors
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DOI：
10.1111/j.1442-9071.2008.001798.x
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发表时间：
2008-07-01
影响因子：
4
通讯作者：
Mackey, David A.
中科院分区：
文献类型：
--
作者：
Mackey, David A.
我们吉利斯是青光眼研究的主要贡献者，特别是假脱叶（XFS），以及斜视，特别是与轴长（AL）有关的斜视。后一项工作涉及将眼睛的几何结构分解为基本组成部分，并使用测量的AL来定制所需的斜视手术量。类似地，寻找青光眼基因需要我们将青光眼分解为其组成措施和相关的风险因素。在过去的14年里，我们在塔斯马尼亚州青光眼遗传研究的数据显示：60%的青光眼病例有家族史; 27%的青光眼大家族成员不知道他们的青光眼家族史;家族性青光眼比散发性青光眼更严重。肌球蛋白突变占原发性开角型青光眼病例的3%。已经确定了一些基因型-表型相关性。值得注意的是，相对于较早的发病年龄、较高的最大记录眼内压和需要手术，Gln 368 Stop突变赋予轻度风险，Thr 377 Met和Gly 252 Arg突变赋予中度风险，而Pro370 Leu突变赋予重度风险。为了确定与青光眼相关的其他基因，我们在双胞胎眼睛研究中检查了正常双胞胎，以确定青光眼异常参数的遗传性-眼内压和杯盘比以及青光眼的混杂因素，如中央角膜厚度，视盘面积，我们已经确定了所有这些的高遗传性，以及5号染色体上与AL相关的基因位点。最近，LOXL 1基因与XFS相关。进一步基因的鉴定将提高我们对青光眼的认识，并允许级联遗传筛查。
WE Gillies was a major contributor to research in glaucoma, notably pseuodexfoliation (XFS), as well as strabismus, particularly in relation to axial length (AL). The latter work involved breaking down the geometry of the eye to its basic components and using the measured AL to tailor the amount of strabismus surgery required. Similarly, the search for glaucoma genes requires us to break down glaucoma into its component measures and associated risk factors. Over the last 14 years, our data from the Glaucoma Inheritance Study in Tasmania have shown the following: that a family history is present in 60% of glaucoma cases; that 27% of members of large glaucoma families were unaware of their family history of glaucoma; and that familial glaucoma is more severe than sporadic glaucoma. Myocilin mutations account for 3% of cases of primary open angle glaucoma. Some genotype-phenotype correlations have been identified. Notably, with respect to earlier age of onset, higher maximum recorded intraocular pressure and need for surgery, the Gln368Stop mutation confers mild risk, Thr377Met and Gly252Arg mutations intermediate risk, and the Pro370Leu mutation severe risk. To identify the other genes associated with glaucoma, we have examined normal twins in the Twins Eye Study to determine the heritability of parameters that are abnormal in glaucoma - intraocular pressure and cup-to-disc ratio and confounding factors for glaucoma such as central corneal thickness, disc area, refraction and AL. We have identified high heritabilities for all of these as well as a gene locus associated with AL on chromosome 5. Recently, the LOXL1 gene was associated with XFS. Identification of further genes will improve our understanding of glaucoma and allow cascade genetic screening.