SQSTM1 Mutations and Glaucoma
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...
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898711/ |
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pubmed-48987112016-06-16 SQSTM1 Mutations and Glaucoma Scheetz, Todd E. Roos, Ben R. Solivan-Timpe, Frances Miller, Kathy DeLuca, Adam P. Stone, Edwin M. Kwon, Young H. Alward, Wallace L. M. Wang, Kai Fingert, John H. Research Article 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. Public Library of Science 2016-06-08 /pmc/articles/PMC4898711/ /pubmed/27275741 http://dx.doi.org/10.1371/journal.pone.0156001 Text en © 2016 Scheetz et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Scheetz, Todd E. Roos, Ben R. Solivan-Timpe, Frances Miller, Kathy DeLuca, Adam P. Stone, Edwin M. Kwon, Young H. Alward, Wallace L. M. Wang, Kai Fingert, John H. |
| spellingShingle |
Scheetz, Todd E. Roos, Ben R. Solivan-Timpe, Frances Miller, Kathy DeLuca, Adam P. Stone, Edwin M. Kwon, Young H. Alward, Wallace L. M. Wang, Kai Fingert, John H. SQSTM1 Mutations and Glaucoma |
| author_facet |
Scheetz, Todd E. Roos, Ben R. Solivan-Timpe, Frances Miller, Kathy DeLuca, Adam P. Stone, Edwin M. Kwon, Young H. Alward, Wallace L. M. Wang, Kai Fingert, John H. |
| author_sort |
Scheetz, Todd E. |
| title |
SQSTM1 Mutations and Glaucoma |
| title_short |
SQSTM1 Mutations and Glaucoma |
| title_full |
SQSTM1 Mutations and Glaucoma |
| title_fullStr |
SQSTM1 Mutations and Glaucoma |
| title_full_unstemmed |
SQSTM1 Mutations and Glaucoma |
| title_sort |
sqstm1 mutations and glaucoma |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898711/ |
| _version_ |
1613591291796389888 |