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 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.
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Todd E
TE
Scheetz
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Ben R
BR
Roos
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Frances
F
Solivan-Timpe
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Kathy
K
Miller
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Adam P
AP
DeLuca
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Edwin M
EM
Stone
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Young H
YH
Kwon
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
Wallace L M
WL
Alward
Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.|Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of America.
Kai
K
Wang
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States of America.
John H
JH
Fingert
D000368:Aged; D018797:Cell Cycle Proteins; D005260:Female; D006801:Humans; D057066:Low Tension Glaucoma / Q000235:genetics* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein / Q000235:genetics* / Q000378:metabolism; D035582:Transcription Factor TFIIIA / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D035582:Transcription Factor TFIIIA; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human