Analysis of myocilin mutations in 1703 glaucoma patients from five different populations
Analysis of myocilin mutations in 1703 glaucoma patients from five different populations
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DOI：
10.1093/hmg/8.5.899
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发表时间：
1999-05-01
影响因子：
3.5
通讯作者：
Stone, EM
中科院分区：
文献类型：
--
作者：
Fingert, JH;Héon, E;Stone, EM
青光眼基因座，GLC 1A，以前被确定在染色体1 q上。该基因座内的一个基因（编码蛋白质myocilin）随后被证明在2-4%的原发性开角型青光眼患者中存在突变。从代表三个种族组的五个不同人群中筛选了总共1703例患者。1284例患者主要来自爱荷华州（727例）、澳大利亚（390例）和加拿大（167例）的白人人群，312例非裔美国人患者来自纽约市，107例亚洲患者来自日本。总的来说，鉴定了61种不同的肌球蛋白序列变异。在61个变异中，21个被判定为可能的致病突变，每个群体中发现携带此类突变的先证者数量为：爱荷华州（4.3%），来自纽约市的非洲裔美国人8/312总体而言，21种突变中有16种（76%）仅在一个人群中发现。观察到的最常见突变Gln 368 Stop见于27/1703（1.6%）青光眼先证者，并且在除日本人外的所有组中至少发现一次。对肌球蛋白基因侧翼遗传标记的研究表明，大多数Gln 368 Stop突变的病例都是来自一个共同的创始人。虽然在五个人群中发现的特定突变不同，但所有人群中肌球蛋白突变的总体频率相似（相似于2-4%），这表明非裔美国人青光眼发病率的增加不是由于肌球蛋白突变的患病率较高。
A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167), A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations, The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3.4%), Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar (similar to 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.