Heterozygous <i>RHO</i> p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors

Wu, Yuan; Guo, Yi; Yi, Junhui; Xu, Hongbo; Yuan, Lamei; Yang, Zhijian; Deng, Hao

doi:10.1042/bsr20182198

Cited by 3 publications

(4 citation statements)

References 42 publications

(52 reference statements)

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“…Moreover, RHO p.P347L is a widely reported mutation in the Japanese, Lithuanian, South African, and Spanish populations ( Fujiki et al, 1992 ; Kucinskas et al, 1999 ; Roberts et al, 2000 ; Fernandez-San Jose et al, 2015 ). RHO p.R135W is a common mutation in the Han-Chinese family ( Wu et al, 2019 ), and RHO p. E181K and p. D190Y are common mutations in the Dutch and Belgian populations ( Nguyen et al, 2021 ). Consistent with previous reports in literature, our study identified p.P347L as one of the two most common pathogenic variants (5 of 36 families; 13.8%).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin

Jung,

Kwak,

Joo

et al. 2023

Front. Genet.

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Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP).Design: We conducted a retrospective, multicenter, observational cohort study.Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea.Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP.Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8–78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6–268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes.Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO-associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin

Jung,

Kwak,

Joo

et al. 2023

Front. Genet.

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“…P23H, the first mutation reported in ADRP ( Dryja et al, 1991 ), is the most common mutation found in rhodopsin in the United States ( Wu et al, 2019 ; Woods and Pfeffer, 2020 ). P23H rhodopsin is a typical example of a class II mutation.…”

Section: Mechanisms Of Rhodopsin-related Retinal Disordersmentioning

confidence: 99%

“…RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Although rare, RP can also be inherited in mitochondrial or digenic forms ( Kim et al, 2012 ; Wu et al, 2014 ; Zhang, 2016 ; Wu et al, 2019 ). This review aims to summarize the progress in studies on the mechanism and therapy for retinal disorders related to rhodopsin mutations, including RP and CSNB.…”

Section: Introductionmentioning

confidence: 99%

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

et al. 2023

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Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations.

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“…Analysis-ready alignment data were acquired by filtering raw reads to remove duplicates and performing local alignment to the hg19 (GRCh37) human reference sequence. Base quality was recalibrated by Picard Mark Duplicates (http://sourceforge.net/projects/picard/), Genome Analysis Toolkit (https://gatk.broadinstitute.org/hc/en-us), and SAM tools (http://samtools.sourceforge.net/) [22]. Single nucleotide variations, insertions, and deletions were identified using the Genome Analysis Toolkit.…”

Section: In Silico Analysesmentioning

confidence: 99%

Whole exome sequencing of a family revealed a novel variant in the CHM gene, c.22delG p.(Glu8Serfs*4), which co-segregated with choroideremia

Dan

Lei

et al. 2020

Bioscience Reports

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Choroideremia is a complex form of blindness-causing retinal degeneration. The aim of the present study was to investigate the pathogenic variant and molecular etiology associated with choroideremia in a Chinese family. All available family members underwent detailed ophthalmological examinations. Whole exome sequencing, bioinformatics analysis, Sanger sequencing, and co-segregation analysis of family members were used to validate sequencing data and confirm the presence of the disease-causing gene variant. The proband was diagnosed with choroideremia on the basis of clinical manifestations. Whole exome sequencing showed that the proband had a hemizygous variant in the CHM gene, c.22delG p. (Glu8Serfs*4), which was confirmed by Sanger sequencing and found to co-segregate with choroideremia. The variant was classified as likely pathogenic and has not previously been described. These results expand the spectrum of variants in the CHM gene, thus potentially enriching the understanding of the molecular basis of choroideremia. Moreover, they may provide insight for future choroideremia diagnosis and gene therapy.

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Heterozygous RHO p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors

Cited by 3 publications

References 42 publications

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

Whole exome sequencing of a family revealed a novel variant in the CHM gene, c.22delG p.(Glu8Serfs*4), which co-segregated with choroideremia

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