PRPF3 gene

Overview

Gene (OMIM No.)	PRPF3 (#607301)
Function of gene/protein	Protein: Pre-mRNA processing factor 3 Involves in pre-mRNA splicing (spliceosome) Stabalisation of the U4/U6•U5 tri-snRNP (mall nuclear ribonucleoprotein particles) Mutations result in altered levels of snRNP, delayed spliceosome assembly and inefficient splicing
Clinical phenotype (OMIM phenotype no.)	Autosomal dominant retinitis pigmentosa: Retinitis pigmentosa 18 (#601414)
Inheritance	Autosomal dominant
Signs for RP	Vessel attenuation Optic disc pallor Mid-peripheral bone spicule pigmentation which progresses to retinal atrophy in later stages RPE mottling Fundus may appear normal in the early stages
Visual function	Autosomal dominant RP Nyctalopia onset usually during 1st to 2nd decade of life Some have later onset of nyctalopia (4th decade of life) Progressive peripheral VF and VA loss ERG responses usually extinguished by 4th decade Patients tend to be myopic Variable expressivity
Systemic features	No extraocular anomalies reported
Key investigations	ERG: absent responses/severe rod-cone dystrophy FAF: Central hyper-AF ring surrounded by diffuse hypo-AF OCT scan to assess outer retinal layer and RPE integrity
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Management of RP
Therapies under research	None at present
Further information	OMIM

Reported variants are located in the C-terminal region.^[1,3]

Růžičková Š, Staněk D. Mutations in spliceosomal proteins and retina degeneration. RNA Biol. 2017;14(5):544-552
Zahid S, Branham K, Schlegel D, et al. Retinal Dystrophy Gene Atlas. Springer; 2018
Zhong Z, Yan M, Sun W, et al. Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa [published correction appears in Sci Rep. 2017 Mar 28;7:45248]. Sci Rep. 2016;6:37840
Vaclavik V, Gaillard MC, Tiab L, Schorderet DF, Munier FL. Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene. Mol Vis. 2010;16:467-475
Inglehearn CF, Tarttelin EE, Keen TJ, et al. A new dominant retinitis pigmentosa family mapping to the RP18 locus on chromosome 1q11-21. J Med Genet. 1998;35(9):788-789
Wada Y, Itabashi T, Sato H, Tamai M. Clinical features of a Japanese family with autosomal dominant retinitis pigmentosa associated with a Thr494Met mutation in the HPRP3 gene. Graefes Arch Clin Exp Ophthalmol. 2004;242(11):956-961

Updated on November 30, 2020