Retinal disorders
Gene: RBP3
Comment on list classification: Promoted to green due to two expert reviews.Created: 3 Jun 2016, 7:40 a.m.
Review from Panagiotis Sergouniotis (Manchester University) June 2, 2016 by email: "I am quite convinced that RBP3 is a bona fide IRD-associated gene. Further to your email, the evidence that substantiates this is:
* Arno et al, IOVS 2015 used exome seq to identify two families with homozygous presumed LOF variants [c.1530T>A, p.(Tyr510*) and c.3454G>T, p.(Glu1152*)]. The phenotype was characteristic and shared among affected individuals.
* Abu-Safieh et al, Genome Res (2013) used 'autozygome guided' exome seq to identify a homozygous presumed LOF variant [(c.1162C>T; p.(Arg388*)] in a sporadic IRD case.
* Li et al, JBC 2013 provided functional evidence of pathogenicity for a homozygous missense change [c.3238G>A, p.(Asp1080Asn)] identified in four affected siblings from a consanguineous family with IRD (originally identified by Den Hollander et al IOVS 2009) .
* The RBP3 protein function and localisation would be in keeping with an IRD-associated gene (interphotoreceptor retinoid binding protein exclusively expressed in photoreceptors & pineal gland). Also, the knockout mouse model has an IRD phenotype.
I think that the data from the Arno paper alone would be sufficient but given that there is further evidence, I would be very comfortable to classify this as 'green' and include it."Created: 3 Jun 2016, 7:39 a.m.
This gene is on the Manchester Genetic Retinal Degeneration Conditions panel (covers known genes for isolated progessive retinal degeneration, Leber congenital amaurosis, macular dystrophy, achromatopsia, congenital stationary night blindness as well as the two most common causes of syndromic blindess Usher and Bardet-Biedl syndromes and additional syndromes including Joubert, Senior-Loken, and Cohen syndrome.Created: 2 Jun 2016, 8:06 a.m.
We have not identified mutations in this gene in a disease-causing state to date. Evidence in the literature suggests this could be a valid gene for the panel but we have insufficient knowledge from our data to qualify this.Created: 1 Jun 2016, 11:12 a.m.
Mode of inheritance
Unknown
Phenotypes
RP
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source NHS GMS was added to RBP3. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
Phenotypes for RBP3 were set to Eye Disorders; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa; ?Retinitis pigmentosa 66, 615233
This gene has been classified as Green List (High Evidence).
Publications for RBP3 were set to Review of the literature from Stephanie Barton - Arno et al (2015) Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy. Invest Ophthalmol Vis Sci. Apr;56(4):2358-65: Two novel homozygous nonsense mutations (c.1530T>A;p.Y510* and c.3454G>T;p.E1152*) in RBP3 were identified in four patients from two families. All four patients had a similar, unusual retinal dystrophy characterized by childhood onset high myopia, generalized rod and cone dysfunction, and an unremarkable fundus appearance. The FAF imaging showed multiple paracentral foci of low autofluorescence in one patient and patchy increased FAF in the region of the vascular arcades in another. The OCT showed loss of outer retinal bands over peripheral macular areas in all 4 cases; Abu-Safieh et al (2013) Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res. Feb;23(2):236-47; NM_002900.2 RBP3 :c.1162C>T; p.(Arg388*) identified in homozygous state in patient with sporadic RP; Li et al (2013) Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP). J Biol Chem. Apr 19;288(16):11395-406: Functional studies to assess pathogenicity of a missense change, D1080N, that was identified in a homozygous state in a patient with ARRP by Den Hollander et al 2009. The mutation abolished IRBP secretion and induced endoplasmic reticulum stress by forming insoluble IRBP-containing complexes via disulfide bonds. Conclude that Loss of normal function and gain of cytotoxic function are the likely mechanisms for retinal degeneration.
This gene has been classified as Amber List (Moderate Evidence).
Model of inheritance for gene RBP3 was set to BIALLELIC, autosomal or pseudoautosomal
RBP3 was added to Posterior segment abnormalitiespanel. Sources: Expert Review Green
RBP3 was created by ellenmcdonagh