Purchase this article with an account.
Nicole C L Noel, Jingyi Ma, Ian M MacDonald; Mutations in RP1L1 are Associated with Stargardt Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3142.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The Retinitis Pigmentosa 1-Like 1 (RP1L1) gene encodes a structural component of the photoreceptor axoneme, which is the core structure of photoreceptor primary cilia. Specific missense mutations in RP1L1 cause occult macular dystrophy (OMD; OMIM 613587), a dominantly inherited cone degenerative disease. Deletions or nonsense variants in RP1L1 have been reported to cause recessive retinitis pigmentosa (RP; OMIM 26800), a rod degeneration. Different types of mutations in RP1L1 can therefore cause both rod and cone degenerative disease. Whether RP1L1 mutations can be implicated in photoreceptor degenerative disease outside of OMD and RP is not known. Here, we assess patient data from the eyeGENE™ database to determine whether mutations in RP1L1 are associated with other cone degenerations.
RP1L1 mutations were assessed in patients with photoreceptor degenerations from the eyeGENE™ database. 52 patients with photoreceptor degeneration and RP1L1 variants were ascertained (38 Stargardt disease, 5 pattern dystrophy, 3 cone-rod dystrophy, 3 RP, 3 OMD). Patients with identified disease-causing variants or with potentially pathogenic variants in genes typically associated with the disease (such as a variant ABCA4 in the case of Stargardt disease) were excluded from study. Mutations were evaluated using mutation pathogenicity predictor programs (PolyPhen-2, MutPred2, and MutationTaster).
PolyPhen-2 appeared to be the most successful program of those used at predicting pathogenicity for missense mutations in RP1L1. This was determined by inputting variants that are known to cause OMD into the programs. MutPred2 and MutationTaster categorized known OMD-causing RP1L1 variants as benign/polymorphisms, while PolyPhen-2 consistently predicted these variants as damaging. Therefore, PolyPhen-2 seems to be the most accurate for predicting pathogenicity of RP1L1 mutations when amino acid sequence is altered. RP1L1 variants were predicted to be pathogenic in one patient diagnosed with Stargardt disease. This patient was compound heterozygous for c.1370C>G (p.Ser457Cys) and c.4396G>T (p.Glu1466*) in RP1L1.
Mutations in RP1L1 do not exclusively cause occult macular dystrophy and retinitis pigmentosa, and have been found, here, to be associated with Stargardt macular degeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only