Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy
| العنوان: | Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy |
|---|---|
| المؤلفون: | Pilar Méndez-Vendrell, Rafael Navarro, Esther Pomares, Borja Corcóstegui, Marina Riera, Sheila Ruiz-Nogales, Víctor Abad-Morales |
| المصدر: | British Journal of Ophthalmology. 104:173-181 |
| بيانات النشر: | BMJ, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Sanger sequencing, medicine.medical_specialty, Retinal pigment epithelium, business.industry, Haplotype, Macular dystrophy, Retinography, medicine.disease, eye diseases, Sensory Systems, Cellular and Molecular Neuroscience, Ophthalmology, symbols.namesake, medicine.anatomical_structure, Retinitis pigmentosa, symbols, Medicine, Missense mutation, business, Exome sequencing |
| الوصف: | PurposeThis 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).MethodsClinical 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.ResultsA 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.ConclusionThis 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. |
| تدمد: | 1468-2079 0007-1161 |
| DOI: | 10.1136/bjophthalmol-2018-313672 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::96282454edd1e1f5bcb2f7b70387cfcf https://doi.org/10.1136/bjophthalmol-2018-313672 |
| رقم الانضمام: | edsair.doi...........96282454edd1e1f5bcb2f7b70387cfcf |
| قاعدة البيانات: | OpenAIRE |
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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.ResultsA 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. 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