Disease Category: autosomal recessive
Patient Population: <20 known
Known Clinical Trials: None known
Treatment Options: None known
Strategies to Preserve Eye Health: Lutein
Institution(s) Conducting Research:
Radboud Univ Med Center
A FACE OF RP
IN THE NEWS
ACADEMIC PAPERS|JOURNAL ARTICLES|PERSONAL STORIES
Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
Johannes Birtel, Tobias Eisenberger, Martin Gliem, Philipp L. Müller, Philipp Herrmann, Christian Betz, Diana Zahnleiter, Christine Neuhaus, Steffen Lenzner, Frank G. Holz, Elisabeth Mangold, Hanno J. Bolz, and Peter Charbel Issa | Scientific Reports | Vol 8, Article No. 4824 | 19 Mar 2018 |
Per 2017 published research, another woman with a non-syndromic INPP5E gene mutation is 57 years-old patient. At the time of the study, she still had 20/20 vision, but increased light sensitivity and decreased visual acuity.
ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting
Melissa C. Humbert, Katie Weihbrecht, Charles C. Searby, Yalan Li, Robert M. Pope, Val C. Sheffield, and Seongjin Seo | PNAS | Vol. 109 (48) | 19691-19696 | 27 Nov 2012 |
The Joubert Syndrome Protein INPP5E Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane
Wenyan Xu, Miaomiao Jin, Ruikun Hu, Hong Wang, Fan Zhang, Shiaulou Yuan and Ying Cao | JSAN | Vol 28 (1) | pgs. 118-129 | Jan 2017 |
Here, we describe a protein–protein interaction network of inositol polyphosphate-5-phosphatase E (INPP5E), a prenylated protein associated with JBTS, and its ciliary targeting mechanisms. INPP5E is targeted to the primary cilium through a motif near the C terminus and prenyl-binding protein phosphodiesterase 6D (PDE6D)-dependent mechanisms.
Together, our data indicate that INPP5E functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns P3 and subsequently stabilizing PtdIns P2 and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.
Prenylated retinal ciliopathy protein RPGR interacts with PDE6δ and regulates ciliary localization of Joubert syndrome-associated protein INPP5E
Kollu N. Rao, Wei Zhang, Linjing Li, Manisha Anand, and Hemant Khanna, Human Molecular Genetics | Vol 25, Issue 20 | pgs. 4533 - 4545 | 15 Oct 2016 |
These results implicate prenylation of RPGR as a critical modification for its localization to cilia and, in turn suggest that trafficking of INPP5E to cilia depends upon the interaction of RPGR with PDE6δ. Finally, our results implicate INPP5E, a novel RPGR-interacting protein, in the pathogenesis of RPGR-associated ciliopathies.
Early onset non-syndromic retinal degeneration due to variants in INPP5E: phenotypic expansion of the ciliary gene previously associated with Joubert syndrome
Riccardo Sangermano, Iris Deitch, Virginie G. Peter, Rola Ba-Abbad, Emily M. Place, Naomi E. Wagner, Anne B. Fulton, Luisa CoutinhoSantos, Boris Rosin, Vincent Dunet, Ala’a Al Talbishi, Eyal Banin, Ana Berta Sousa, Mariana Neves, Anna Larson, Mathieu Quinodoz, Michel Michaelides, Tamar Ben-Yosef, Eric A. Pierce, Carlo Rivolta, Andrew R. Webster, Gavin Arno, Dror Sharon, Rachel M. Huckfeldt, Kinga M. Bujakowska | medRxiv | 26 Aug 2020 |
Our study reveals a novel disease association of variants in INPP5E with non-syndromic retinal degeneration. We describe 12 mostly non-syndromic families, in which 18 affected members carried bi-allelic likely pathogenic variants in INPP5E resulting in phenotypes of LCA and RCD (or retinitis pigmentosa). Of the 14 alleles, 12 were novel and mainly resulting in missense changes of conserved amino acid residues in the phosphatase catalytic domain (Fig. 2A)
The Major Ciliary Isoforms of RPGR Build Different Interaction Complexes with INPP5E and RPGRIP1L
Christine Vössing, Paul Atigbire, Jannis Eilers, Fenja Markus, Knut Stieger, Fei Song, and John Neidhardt | International Journal Molecular Sciences | 22 Apr 2021 | pg. 3583 |
X-linked retinitis pigmentosa (XLRP) is frequently caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. . . . Interestingly, interaction complexes with INPP5E or RPGRIP1L were only detectable with isoform RPGRex1-19, but not with RPGRskip14/15, demonstrating distinct functional properties of the major RPGR isoforms in spite of their similar subcellular localization. Our findings lead to the conclusion that protein binding sites within RPGR are mediated through alternative splicing.