July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The spectrum of RP1 mutations confirms a dominant negative disease mechanism
Author Affiliations & Notes
  • Anika Nanda
    Oxford Eye Hospital, Oxford, United Kingdom
  • Michelle McClements
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Morag Shanks
    Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • Robert MacLaren
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships   Anika Nanda, None; Michelle McClements, None; Morag Shanks, None; Robert MacLaren, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2329. doi:https://doi.org/
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      Anika Nanda, Michelle McClements, Morag Shanks, Robert MacLaren; The spectrum of RP1 mutations confirms a dominant negative disease mechanism. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2329. doi: https://doi.org/.

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

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Purpose : Mutations in the photoreceptor gene RP1 may lead to recessive or dominantly inherited retinitis pigmentosa (RP). Since the dominantly inherited phenotype is considerably milder than recessive cases, it raises the possibility that it could arise by haploinsufficiency. We therefore assessed a cohort of RP patients with confirmed mutations in RP1 in order to examine the genetic basis of the mutations in more detail.

Methods : A retrospective review of 14 patients, aged between 36 and 84, identified with RP1 mutations confirmed by Sanger genetic sequencing. All patients underwent full ophthalmic examination, including visual acuities with auto fluorescence imaging and optical coherence tomography.

Results : Two patients had homozygous mutations in RP1 and had severe early onset retinal degeneration (p.Glu1526X and p.Ser486fs). Twelve patients had dominantly inherited retinitis pigmentosa presenting in adult life with a rod-cone dystrophy phenotype. All mutations were in exon 4 of the RP1 gene and would be predicted to generate truncated RP1 protein as follows: p.Leu866Lysfs*7x2, p.Ile725Argfs*6, p.Gln917*, p.Ser734*x2, p.Leu762Tyrfs*17x2, p.Arg677*, p.Arg872Thrfs*2x2 and p.Gln679*. No dominantly inherited mutations were identified in upstream exons 1-3.

Conclusions : The spectrum of RP1 mutations in dominantly inherited RP is confined to exon 4 from which truncated transcripts would be predicted to generate mutant protein. The finding of exon 4 mutations as a cause of severe RP may be indicative of homozygous dominant mutations that could make genetic counselling difficult.

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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