July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Mutations in RP1L1 are Associated with Stargardt Macular Degeneration
Author Affiliations & Notes
  • Nicole C L Noel
    Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
  • Jingyi Ma
    University of Alberta, Edmonton, Alberta, Canada
  • Ian M MacDonald
    Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada
    Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
  • Footnotes
    Commercial Relationships   Nicole Noel, None; Jingyi Ma, None; Ian MacDonald, None
  • Footnotes
    Support  Alberta Innovates Graduate Student Scholarship
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3142. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : 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.

Methods : 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).

Results : 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.

Conclusions : 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.


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