Disease Category: autosomal recessive
Known Clinical Trials: none
Part of Research Study: yes
Treatment Options: none
Targeted Strategies to Preserve Eye Health: none
Institution(s) Conducting Research: Radboud Univ Med Ctr
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Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy
ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting
The Joubert Syndrome Protein INPP5E Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane
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.
Melissa C. Humbert, Katie Weihbrecht, Charles C. Searby, Yalan Li, Robert M. Pope, Val C. Sheffield, and Seongjin Seo, 109 (48) 19691-19696, 27 Nov 2012.
Wenyan Xu, Miaomiao Jin, Ruikun Hu, Hong Wang, Fan Zhang, Shiaulou Yuan and Ying Cao, Vol 28 (1), pgs. 118-129, January 2017.
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.
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(3,4,5)P3 and subsequently stabilizing PtdIns(4,5)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.
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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.