+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Rom1 converts Y141C-Prph2-associated pattern dystrophy to retinitis pigmentosa

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Mutations in peripherin 2 ( PRPH2), also known as retinal degeneration slow/ RDS, lead to various retinal degenerations including retinitis pigmentosa (RP) and macular/pattern dystrophy (MD/PD). PRPH2-associated disease is often characterized by a phenotypic variability even within families carrying the same mutation, raising interest in potential modifiers. PRPH2 oligomerizes with its homologue rod outer segment (OS) membrane protein 1 (ROM1), and non-pathogenic PRPH2/ROM1 mutations, when present together, lead to digenic RP. We asked whether ROM1 could modify the phenotype of a PRPH2 mutation associated with a high degree of intrafamilial phenotypic heterogeneity: Y141C. In vitro, Y141C-Prph2 showed signs of retention in the endoplasmic reticulum (ER), however co-expression with Rom1 rescued this phenotype. In the heterozygous Y141C knockin mouse model ( Prph2 Y/+ ), Y141C-Prph2 and Rom1 formed abnormal complexes but were present at normal levels. Abnormal complexes were eliminated in the absence of Rom1 ( Prph2 Y/+/Rom1 -/- ) and total Prph2 levels were reduced to those found in the haploinsufficient Prph2 +/- RP model. The biochemical changes had functional and structural consequences; while Prph2 Y/+  animals exhibited a cone-rod electroretinogram defect, Prph2 Y/+/Rom1 -/- animals displayed a rod-dominant phenotype and OSs similar to those seen in the Prph2 +/- . These data show that ablation of Rom1 results in the conversion of an MD/PD phenotype characterized by cone functional defects and the formation of abnormal Prph2/Rom1 complexes to an RP phenotype characterized by rod-dominant functional defects and reductions in total Prph2 protein. Thus one method by which ROM1 may act as a disease modifier is by contributing to the large variability in PRPH2-associated disease phenotypes.

          Related collections

          Author and article information

          Hum Mol Genet
          Hum. Mol. Genet
          Human Molecular Genetics
          Oxford University Press
          01 February 2017
          04 January 2017
          01 February 2018
          : 26
          : 3
          : 509-518
          [1 ]Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
          [2 ]Department of Biomedical Engineering, University of Houston, Houston, TX, USA
          Author notes
          [* ]To whom correspondence should be addressed at: Muna I. Naash, Ph.D., John S. Dunn Professor of Biomedical Engineering, Department of Biomedical Engineering, University of Houston, 3517 Cullen Blvd. Room 2011, Houston, TX 77204-5060, USA. Tel: 713-743-1651; E-mail: mnaash@ 123456central.uh.edu

          These two authors contributed equally to this work.

          PMC6075606 PMC6075606 6075606 ddw408
          © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
          Page count
          Pages: 10
          Funded by: National Eye Institute 10.13039/100000053
          Award ID: R01EY010609-MIN
          Funded by: Foundation Fighting Blindness (MIN), the Oklahoma Center for the Advancement of Science and Technology
          Award ID: SMC, HR14-150
          Funded by: Presbyterian Health Foundation (SMC)


          Comment on this article