Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma
Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma
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DOI：
10.1016/s0002-9394(00)00536-5
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发表时间：
2000-08-01
影响因子：
4.2
通讯作者：
Richards, JE
中科院分区：
文献类型：
--
作者：
Shimizu, S;Lichter, PR;Richards, JE
目的：筛查原发性开角型青光眼人群中编码小梁网诱导型糖皮质激素反应蛋白 (TIGR)（也称为肌纤蛋白 (MYOC)）的基因突变。方法：收集原发性开角型青光眼研究对象及其亲属的眼科信息。通过对 TIGR/MYOC 编码序列和剪接位点进行测序，对 74 个原发性开角型青光眼先证者进行了突变筛查。 结果：在 23 个家系中，我们检测到 13 个非同义序列变化，其中 9 个似乎是可能导致或促成原发性开角型青光眼的突变。两种突变 Arg272Gly 和 Ile499Ser 以及一种非同义序列变体 Asn57Asp 是新的。我们在 25 名青少年青光眼先证者中的 9 名（36%）和 49 名成人青光眼先证者中的 2 名（4%）中发现了突变。对家庭而不是个体先证者的年龄分类显示，9 个患有严格青少年原发性开角型青光眼的家庭中有 3 个（33%）存在突变，而 39 个患有严格成人发病的原发性开角型青光眼的家庭中没有突变（0%）。在混合发病的原发性开角型青光眼家族中，包括青少年原发性开角型青光眼和成人发病的原发性开角型青光眼病例，我们在 26 个家族中的 8 个家族中发现了突变 (31%)。结论：我们的数据表明，Gly252Arg、Arg272Gly、Glu323Lys、Gln368STOP、Pro370Leu、Thr377Met、 Val42Phe、Ile477Asn 和 Ile499Ser 可能在常染色体显性原发性开角型青光眼的病因中发挥作用。我们发现，混合发病的原发性开角型青光眼家庭中的 TIGR/MYOC 突变多于严格成人发病的原发性开角型青光眼的家庭，这意味着家庭中是否存在患有青少年原发性开角型青光眼的亲属，可以作为确定 TIGR/MYOC 突变患病率较高的成人发病的原发性开角型青光眼人群子集的基础。为了解决这个问题，并完善对这些年龄定义的亚人群中突变发生率的估计，需要对完全通过成人发病的原发性开角型青光眼先证者确定的更大人群进行前瞻性研究。 (C) 2000 年，Elsevier Science Inc. 保留所有权利。
PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC).METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites.RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). Tn families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%).CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val42Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed. (C) 2000 by Elsevier Science Inc. All rights reserved.