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Expanding the retinal phenotype of RP1 : from retinitis pigmentosa to a novel and singular macular dystrophy.
- Source :
-
The British journal of ophthalmology [Br J Ophthalmol] 2020 Feb; Vol. 104 (2), pp. 173-181. Date of Electronic Publication: 2019 May 11. - Publication Year :
- 2020
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Abstract
- Purpose: This study aimed to identify the underlying genetic cause(s) of inherited retinal dystrophy (IRD) in 12 families of Kuwaiti origin affected by macular dystrophy and four Spanish patients affected by retinitis pigmentosa (RP).<br />Methods: Clinical diagnoses were based on standard ophthalmic evaluations (best-corrected visual acuity, retinography, fundus autofluorescence imaging, optical coherence tomography, electroretinography and visual field tests). Panel-based whole exome sequencing was used to simultaneously analyse 224 IRD genes in one affected member of each family. The putative causative variants were confirmed by Sanger sequencing and cosegregation analyses. Haplotype analysis was performed using single nucleotide polymorphisms.<br />Results: A homozygous missense mutation c.606C>A (p.Asp202Glu) in RP1 was found to be the molecular cause of IRD in all 12 families from Kuwait. These patients exhibited comparable symptoms, including progressive decline in visual acuity since adolescence. Fundus autofluorescence images revealed bilateral macular retinal pigment epithelium disturbances, with neither perimacular flecks nor peripheral alterations. A shared haplotype spanning at least 1.1 Mb was identified in all families, suggesting a founder effect. Furthermore, RP1 variants involving nonsense and/or frameshifting mutations (three of them novel) were identified in three Spanish autosomal-recessive RP families and one dominant RP pedigree.<br />Conclusion: This study describes, for the first time, a macular dystrophy phenotype caused by an RP1 mutation; establishing a new genotype-phenotype correlation in this gene, expanding its mutation spectrum and further highlighting the clinical heterogeneity associated with IRD.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Adolescent
Adult
Electroretinography
Eye Proteins genetics
Female
Genetic Association Studies
Genetic Predisposition to Disease genetics
Humans
Macular Degeneration physiopathology
Male
Middle Aged
Mutation
Pedigree
Phenotype
Retinitis Pigmentosa physiopathology
Visual Acuity
Visual Field Tests
Young Adult
Macular Degeneration genetics
Microtubule-Associated Proteins genetics
Retinitis Pigmentosa genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1468-2079
- Volume :
- 104
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The British journal of ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 31079053
- Full Text :
- https://doi.org/10.1136/bjophthalmol-2018-313672