June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Novel missense mutations in PRPF6 cause autosomal dominant retinitis pigmentosa with incomplete penetrance and impairment of PRPF6 protein localization within the nucleus
Author Affiliations & Notes
  • Guillaume OLIVIER
    INSERM, Montpellier, France
  • Beatrice BOCQUET
    INSERM, Montpellier, France
    Centre Hospitalier Universitaire, Montpellier, France
  • Carlo Rivolta
    Institute for Molecular and Clinical Ophthalmology, University, Basel, Switzerland
  • Ervann Andreo
    Université, Montpellier, France
  • Agnes Muller
    Université, Montpellier, France
  • Christian Hamel
    INSERM, Montpellier, France
    Centre Hospitalier Universitaire, Montpellier, France
  • Alice MASUREL
    Centre Hospitalier Universitaire, Dijon, France
  • Catherine P Creuzot Garcher
    Centre Hospitalier Universitaire, Dijon, France
  • Laurence FAIVRE
    Centre Hospitalier Universitaire, Dijon, France
  • Isabelle Anne Meunier
    Centre Hospitalier Universitaire, Montpellier, France
  • Gael Manes
    Université, Montpellier, France
  • Footnotes
    Commercial Relationships   Guillaume OLIVIER, None; Beatrice BOCQUET, None; Carlo Rivolta, None; Ervann Andreo, None; Agnes Muller, None; Christian Hamel, None; Alice MASUREL, None; Catherine Creuzot Garcher, None; Laurence FAIVRE, None; Isabelle Meunier, None; Gael Manes, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2401. doi:
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      Guillaume OLIVIER, Beatrice BOCQUET, Carlo Rivolta, Ervann Andreo, Agnes Muller, Christian Hamel, Alice MASUREL, Catherine P Creuzot Garcher, Laurence FAIVRE, Isabelle Anne Meunier, Gael Manes; Novel missense mutations in PRPF6 cause autosomal dominant retinitis pigmentosa with incomplete penetrance and impairment of PRPF6 protein localization within the nucleus. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2401.

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

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Abstract

Purpose : To characterize clinically and genetically two families with autosomal dominant retinitis pigmentosa (adRP) with new causative mutations in PRPF6, a gene described to be associated with this condition in a single study.

Methods : A large adRP and sporadic RP cohort was screened for mutations using targeted next-generation sequencing. Clinical investigations included visual acuity and visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, full-fields and multifocal electroretinogram (ERG) recording. Cellular localization of GFP-tagged wild-type or mutated PRPF6 in HEK293 transfected cells was observed by confocal microscopy.

Results : Two heterozygous mutations c.680C>T (p.Thr227Met) and c.514C>T (p.Arg172Trp) in PRPF6 were identified in an adRP family and in a sporadic RP patient, respectively. Both variants segregated with the disease phenotype and were predicted to be pathogenic. An asymptomatic heterozygous carrier of the p.Arg172Trp mutation was also identified. In HEK293 transfected cells, an abnormal accumulation of the two mutated GFP-PRPF6, but not wild-type, within Cajal bodies was observed.

Conclusions : We identified two novel causative mutations in PRPF6, responsible for autosomal dominant retinitis pigmentosa with variation of penetrance. Presence of asymptomatic carriers is common among patients with adRP, especially when the cause of the disease is due to a mutation in splicing factors’ genes. The two mutations identified lead to a mislocalization of the PRPF6 protein within the nucleus, which could indicate a possible alteration in the assembly or recycling of the tri-snRNP complex of the spliceosome.

This is a 2020 ARVO Annual Meeting abstract.

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