Phenotypic Variation Including Retinitis Pigmentosa, Pattern Dystrophy, and Fundus Flavimaculatus in a Single Family With a Deletion of Codon 153 or 154 of the Peripherin/RDS Gene

Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

“…However, we did not identify any clear genotype–phenotype correlation in our cohort, which is similar to the Japanese cohort described by Oishi et al [ 35 ]. There was phenotypic variability between unrelated patients carrying the same PRPH2 variant, consistent with previous reports in the literature [ 15 , 48 ]. The most frequently detected variant in our cohort, c.659G>A p.(Arg220Gln), was associated with PSPD and AVMD phenotypes.…”

Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

“…However, we did not identify any clear genotype–phenotype correlation in our cohort, which is similar to the Japanese cohort described by Oishi et al [ 35 ]. There was phenotypic variability between unrelated patients carrying the same PRPH2 variant, consistent with previous reports in the literature [ 15 , 48 ]. The most frequently detected variant in our cohort, c.659G>A p.(Arg220Gln), was associated with PSPD and AVMD phenotypes.…”

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa

“…However, interestingly, two patients with the same p.G267S sequence change demonstrated markedly different phenotypes. Such variation in retinal phenotype has been well described before in monogenetic retinal diseases [Weleber et al, 1993]. FBLN5 ARMD can therefore also be a cause of choroidal neovascularization in the absence of drusen.…”

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders

“…To mirror the human condition, the K153∆ knockin model was generated by deleting AAA at position 153 site, resulting in a mutant protein lacking on of the two lysines. As a result, this mouse line aligns with both the initial patient report referring to the deletion of 153/154 19 , and the updated information in the Leiden Open Variation Database (LOVD) and in recent literature, where the mutation is identified as c.461_463del, p.Lys154del (db-ID PRPH2_000084) 69 . This mouse line, K153del, has been previously characterized 13 .…”

“…In this study, we demonstrate that modifying the RHO/PRPH2 ratio in favor of PRPH2 positively impacts the disease phenotype in previously characterized knockin mouse models expressing the patient pathogenic variants c.461_463del, p.Lys154del 19 (herein called K153∆ for the knockin mouse model 13 ) and c.422 A > G, p.Tyr141Cys 22 , 23 (herein called Y141C for the knockin mouse model 14 ) in PRPH2 . Proof-of-concept studies presented here revealed that reducing one allele of Rho in the heterozygous models improves photoreceptor ultrastructure and physiological function.…”

Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

“…However, we did not identify any clear genotype–phenotype correlation in our cohort, which is similar to the Japanese cohort described by Oishi et al [ 35 ]. There was phenotypic variability between unrelated patients carrying the same PRPH2 variant, consistent with previous reports in the literature [ 15 , 48 ]. The most frequently detected variant in our cohort, c.659G>A p.(Arg220Gln), was associated with PSPD and AVMD phenotypes.…”

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa

“…However, interestingly, two patients with the same p.G267S sequence change demonstrated markedly different phenotypes. Such variation in retinal phenotype has been well described before in monogenetic retinal diseases [Weleber et al, 1993]. FBLN5 ARMD can therefore also be a cause of choroidal neovascularization in the absence of drusen.…”

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders

“…To mirror the human condition, the K153∆ knockin model was generated by deleting AAA at position 153 site, resulting in a mutant protein lacking on of the two lysines. As a result, this mouse line aligns with both the initial patient report referring to the deletion of 153/154 19 , and the updated information in the Leiden Open Variation Database (LOVD) and in recent literature, where the mutation is identified as c.461_463del, p.Lys154del (db-ID PRPH2_000084) 69 . This mouse line, K153del, has been previously characterized 13 .…”

“…In this study, we demonstrate that modifying the RHO/PRPH2 ratio in favor of PRPH2 positively impacts the disease phenotype in previously characterized knockin mouse models expressing the patient pathogenic variants c.461_463del, p.Lys154del 19 (herein called K153∆ for the knockin mouse model 13 ) and c.422 A > G, p.Tyr141Cys 22 , 23 (herein called Y141C for the knockin mouse model 14 ) in PRPH2 . Proof-of-concept studies presented here revealed that reducing one allele of Rho in the heterozygous models improves photoreceptor ultrastructure and physiological function.…”

Genotype–Phenotype Correlations in PRPH2 Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK

“…However, we did not identify any clear genotype–phenotype correlation in our cohort, which is similar to the Japanese cohort described by Oishi et al [ 35 ]. There was phenotypic variability between unrelated patients carrying the same PRPH2 variant, consistent with previous reports in the literature [ 15 , 48 ]. The most frequently detected variant in our cohort, c.659G>A p.(Arg220Gln), was associated with PSPD and AVMD phenotypes.…”

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa

“…However, interestingly, two patients with the same p.G267S sequence change demonstrated markedly different phenotypes. Such variation in retinal phenotype has been well described before in monogenetic retinal diseases [Weleber et al, 1993]. FBLN5 ARMD can therefore also be a cause of choroidal neovascularization in the absence of drusen.…”

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders

“…To mirror the human condition, the K153∆ knockin model was generated by deleting AAA at position 153 site, resulting in a mutant protein lacking on of the two lysines. As a result, this mouse line aligns with both the initial patient report referring to the deletion of 153/154 19 , and the updated information in the Leiden Open Variation Database (LOVD) and in recent literature, where the mutation is identified as c.461_463del, p.Lys154del (db-ID PRPH2_000084) 69 . This mouse line, K153del, has been previously characterized 13 .…”

“…In this study, we demonstrate that modifying the RHO/PRPH2 ratio in favor of PRPH2 positively impacts the disease phenotype in previously characterized knockin mouse models expressing the patient pathogenic variants c.461_463del, p.Lys154del 19 (herein called K153∆ for the knockin mouse model 13 ) and c.422 A > G, p.Tyr141Cys 22 , 23 (herein called Y141C for the knockin mouse model 14 ) in PRPH2 . Proof-of-concept studies presented here revealed that reducing one allele of Rho in the heterozygous models improves photoreceptor ultrastructure and physiological function.…”