Mutation analysis of the genes associated with anterior segment dysgenesis, microcornea and microphthalmia in 257 patients with glaucoma
Mutation analysis of the genes associated with anterior segment dysgenesis, microcornea and microphthalmia in 257 patients with glaucoma
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DOI：
10.3892/ijmm.2015.2325
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发表时间：
2015-10-01
影响因子：
5.4
通讯作者：
Zhang, Qingjiong
中科院分区：
文献类型：
--
作者：
Huang, Xiaobo;Xiao, Xueshan;Zhang, Qingjiong
遗传因素在青光眼的发展中起着重要作用;然而，在大多数患者中，确切的遗传缺陷仍有待确定。青光眼常见于眼前段发育不全（ASD）、小角膜或小眼球的患者。本研究旨在检测257例青光眼患者中与房间隔缺损、小角膜和小眼球相关的基因的潜在突变。在46个基因中，有43个基因的变异与ASD、小角膜或小眼症有关，可在全外显子组测序中获得。在多步生物信息学分析后选择43个基因中的候选变体，并随后通过桑格测序确认。通过分离分析和对照分析进一步验证确认的变体。总体而言，从全外显子组测序中选择了70个候选变体，其中53个（75.7%）通过桑格测序确认。根据生物信息学分析和对照分析，53例中共有27例被认为具有潜在致病性。在这27个基因中，6个在BEST 1中鉴定，4个在EYA 1中鉴定，3个在GDF 6中鉴定，2个在BMP 4中鉴定，2个在BMPBA 4中鉴定，2个在HCCS中鉴定，并且在BMPAA、BMPGC、BMPGD、COL 4A 1、FOXC 1、GJA 8、PITX 2和SHH中各鉴定1个。257例患者中有28例（10.9%）检测到27种变异，包括125例原发性开角型青光眼患者中的11例和132例原发性闭角型青光眼患者中的17例。这些基因的变异可能是原发性青光眼的潜在危险因素。对不同人群中的其他患者进行仔细的临床观察和分析，预计将进一步促进这些发现。
Genetic factors have an important role in the development of glaucoma; however, the exact genetic defects remain to be identified in the majority of patients. Glaucoma is frequently observed in patients with anterior segment dysgenesis (ASD), microcornea or microphthalmia. The present study aimed to detect the potential mutations in the genes associated with ASD, microcornea and microphthalmia in 257 patients with glaucoma. Variants in 43 of the 46 genes, which are associated with ASD, microcornea or microphthalmia, were available in whole-exome sequencing. Candidate variants in the 43 genes were selected following multi-step bioinformatic analysis and were subsequently confirmed by Sanger sequencing. Confirmed variants were further validated by segregation analysis and analysis of controls. Overall, 70 candidate variants were selected from whole-exome sequencing, of which 53 (75.7%) were confirmed by Sanger sequencing. In total, 27 of the 53 were considered potentially pathogenic based on bioinformatic analysis and analysis of controls. Of the 27, 6 were identified in BEST1, 4 in EYA1, 3 in GDF6, 2 in BMP4, 2 in CRYBA4, 2 in HCCS, and 1 in each of CRYAA, CRYGC, CRYGD, COL4A1, FOXC1, GJA8, PITX2 and SHH. The 27 variants were detected in 28 of 257 (10.9%) patients, including 11 of 125 patients with primary open-angle glaucoma and 17 of 132 patients with primary angle-closure glaucoma. Variants in these genes may be a potential risk factor for primary glaucoma. Careful clinical observation and analysis of additional patients in different populations are expected to further these findings.