SQSTM1 Mutations and Glaucoma.
SQSTM1 Mutations and Glaucoma.
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DOI：
10.1371/journal.pone.0156001
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Fingert JH
中科院分区：
文献类型：
--
作者：
Scheetz TE;Roos BR;Solivan-Timpe F;Miller K;DeLuca AP;Stone EM;Kwon YH;Alward WL;Wang K;Fingert JH
青光眼是世界上最常见的不可逆性失明的原因。青光眼的一个子集，正常眼压性青光眼（NTG）在没有高眼内压的情况下发生。视神经磷酸酶（OPTN）和TANK结合激酶1（TBK1）两个基因的突变导致家族性NTG，并在分解代谢细胞过程自噬中发挥已知作用。TKB1编码一种磷酸化OPTN的激酶，OPTN是一种自噬受体，最终激活自噬。隔离体（SQSTM 1）基因也编码自噬受体，也是TBK1磷酸化的靶点。因此，我们假设SQSTM 1的突变也可能导致NTG。我们通过使用桑格测序在NTG患者（n = 308）和匹配对照组（n = 157）中搜索导致肿瘤的突变来验证这一假设。还使用全外显子组测序分析了另外1098个群体对照样品。共检测到17个非同义突变，当单独分析或作为一组时，这些突变在病例和对照之间没有显著偏斜（p > 0.05）。这些数据表明SQSTM 1突变不是NTG的常见原因。
Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG.