Logo image
SQSTM1 Mutations and Glaucoma
Journal article   Open access   Peer reviewed

SQSTM1 Mutations and Glaucoma

Todd E Scheetz, Ben R Roos, Frances Solivan-Timpe, Kathy Miller, Adam P DeLuca, Edwin M Stone, Young H Kwon, Wallace L M Alward, Kai Wang and John H Fingert
PloS one, Vol.11(6), pp.e0156001-e0156001
2016
DOI: 10.1371/journal.pone.0156001
PMCID: PMC4898711
PMID: 27275741
url
https://doi.org/10.1371/journal.pone.0156001View
Published (Version of record) Open Access

Abstract

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.
Low Tension Glaucoma - genetics Humans Protein-Serine-Threonine Kinases - genetics Transcription Factor TFIIIA - genetics Male Low Tension Glaucoma - metabolism Transcription Factor TFIIIA - metabolism Sequestosome-1 Protein - genetics Female Aged Mutation Sequestosome-1 Protein - metabolism Protein-Serine-Threonine Kinases - metabolism

Details

Metrics

Logo image