Novel Genes Involved In Etiopathogenesis Of Retinitis Pigmentosa Orphan Forms

Luigi Donato, Rita Lauro, Concetta Scimone, Rosalia D’Angelo, Alessandra Costa, Alessandro Calamuneri, Antonina Sidoti


Retinitis Pigmentosa is a rare genetic disease affecting the retina, characterized by the progressive degeneration of rods and cones photoreceptors. The disease is considered one of the main causes of visual impairment and blindness, affecting from 1/9000 to 1/750 people according to their geographical localization. More than 80 genes have been described as causative of Retinitis Pigmentosa, even if there are the so called “orphan forms” showing the same phenotipic condition of RP patients, in the absence of mutations in the already known causative genes. Since RP is a very heterogeneous disorder, it is important to clarify the possible involvement of other genes and their eventual role in the etiopathogenesis of RP orphan forms.


  1. O’Neal TB, Luther EE. Retinitis Pigmentosa. StatPearls2019.
  2. NaKH, KimHJ, Kim KH, HanS, KimS, HannHJ, Ahn HS. Prevalence, Age at Diagnosis, Mortality, and Cause of Death in Retinitis Pigmentosa in Korea—A Nationwide Population-based Study. American Journal of Ophthalmology 2017;176:157-165
  3. 2. Newman A M, Gallo N B, Hancox LS, Miller NJ, Radeke CM, Maloney M A, Cooper JB, Hageman GS, Anderson DH, Johnson LV, Radeke MJ. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks. Genome Medicine 2012;4:16.
  4. Bravo-Gil N, González-del Pozo M, Martín-Sánchez M, Méndez-Vidal C, Rodríguez-de la Rúa E, Borrego S, Antiñolo G. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases.  Sci Rep 2017;7:41937
  5. Hamel  C, Retinitis pigmentosa. Orphanet J Rare Dis2006;1:40
  6. McIntyre JC, Hege M, Berbary N. Trafficking of ciliary G protein-coupled receptors. Methods in Cell Biology 2016;132:35-54
  7. KozminskiKG, JohnsonKA, ForscherP, RosenbaumJL. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci USA 1993;90:5519–5523
  8. Marshall WF, Rosenbaum JL. Intraflagellar transport balances continuous turnover of outer doublet microtubules: implications for flagellar length control. J Cell Biol 2001;155:405
  9. Rosenbaum JL, Witman GB. Intraflagellar transport. Nature Reviews Molecular Cell Biology 2002;3:813–825
  10. Taschner M, Lorentzen E. The Intraflagellar Transport Machinery. US National Library of Medicine 2016;3:8
  11. Li L, Yildiz, Anand M, Khanna H. Photoreceptor Sensory Cilium and Associated Disorders. Ocular Diseases 2012
  12. Deane JA, Cole DG, Seeley ES, Diener DR, Rosenbaum JL. Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles. Curr. Bio2001;11:1586–1590
  13. Tsao CC, Gorovsky MA. Tetrahymena IFT122A is not essential for cilia assembly but plays a role in returning IFT proteins from the ciliary tip to the cell body. J. Cell Sci 2008;121:428–436
  14. Boubakri M, Chaya T, Hirata H, Kajimura N. Loss of IFT122, Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Two to Inefficient Opsin Transport. J Biol Chem 2016;291:24465–24474

Mukhopadhyay S, Wen X, , Chih B, Nelson CD, Lane WS, Scales SJ, Jackson PK.TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes & development 2010;24:2180-93.