scholarly journals Novel deletion in the pre-mRNA splicing genePRPF31 causes autosomal dominant retinitis pigmentosa in a large Chinese family

2003 ◽  
Vol 121A (3) ◽  
pp. 235-239 ◽  
Author(s):  
Lejin Wang ◽  
Michael Ribaudo ◽  
Kanxing Zhao ◽  
Ning Yu ◽  
Qiuyun Chen ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Mrna Splicing ◽  
Chinese Family ◽  
Autosomal Dominant Retinitis Pigmentosa

Novel rhodopsin mutation in a Chinese family with autosomal dominant retinitis pigmentosa

2001 ◽  
Vol 22 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Kanxing Zhao ◽  
Shihong Xiong ◽  
Li Wang ◽  
Lejin Wang ◽  
Yun Cui ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Autosomal Dominant Retinitis Pigmentosa

scholarly journals Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

2017 ◽  
Author(s):  
Adriana Buskin ◽  
Lili Zhu ◽  
Valeria Chichagova ◽  
Basudha Basu ◽  
Sina Mozaffari-Jovin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Retinitis Pigmentosa ◽  
Gene Editing ◽  
Autosomal Dominant ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Patient Specific ◽  
Rpe Cells ◽  
Autosomal Dominant Retinitis Pigmentosa

SummaryMutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To understand the molecular basis of this phenotype, we have generated RP type 11 (PRPF31-mutated) patient-specific retinal organoids and retinal pigment epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing of genes encoding pre-mRNA splicing proteins occurred in patient-specific retinal cells and Prpf31+/− mouse retinae, but not fibroblasts and iPSCs, providing mechanistic insights into retinal-specific phenotypes of PRPFs. RPE was the most affected, characterised by loss of apical-basal polarity, reduced trans-epithelial resistance, phagocytic capacity, microvilli, and cilia length and incidence. Disrupted cilia morphology was observed in patient-derived-photoreceptors that displayed progressive features associated with degeneration and cell stress. In situ gene-editing of a pathogenic mutation rescued key structural and functional phenotypes in RPE and photoreceptors, providing proof-of-concept for future therapeutic strategies.eTOCPRPF31 is a ubiquitously expressed pre-mRNA processing factor that when mutated causes autosomal dominant RP. Using a patient-specific iPSC approach, Buskin and Zhu et al. show that retinal-specific defects result from altered splicing of genes involved in the splicing process itself, leading to impaired splicing, loss of RPE polarity and diminished phagocytic ability as well as reduced cilia incidence and length in both photoreceptors and RPE.HighlightsSuccessful generation of iPSC-derived RPE and photoreceptors from four RP type 11 patientsRPE cells express the mutant PRPF31 protein and show the lowest expression of wildtype proteinPRPF31 mutations result in altered splicing of genes involved in pre-mRNA splicing in RPE and retinal organoidsPrpf31 haploinsufficiency results in altered splicing of genes involved in pre-mRNA splicing in mouse retinaRPE cells display loss of polarity, reduced barrier function and phagocytosisPhotoreceptors display shorter and fewer cilia and degenerative featuresRPE cells display most abnormalities suggesting they might be the primary site of pathogenesisIn situ gene editing corrects the mutation and rescues key phenotypes

scholarly journals Identification of a novel RHO heterozygous nonsense mutation in a Chinese family with autosomal dominant retinitis pigmentosa

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Liu ◽  
Ruru Guo ◽  
Huijie Hao ◽  
Jian Ji
Keyword(s):  
Retinitis Pigmentosa ◽  
Nonsense Mutation ◽  
Autosomal Dominant ◽  
Bioinformatics Analysis ◽  
Molecular Genetic ◽  
Chinese Family ◽  
Graphic System ◽  
Multiple Sequence ◽  
Target Region ◽  
Autosomal Dominant Retinitis Pigmentosa

Abstract Background To explore the molecular genetic cause of a four-generation autosomal dominant retinitis pigmentosa family in China. Methods Targeted region sequencing was performed to detect the potential mutation, and Sanger sequencing was used to validate the mutation. Multiple sequence alignment from different species was performed by CLUSTALW. The structures of wild-type and the mutant RHO were modeled by Swiss-Model Server and shown using a PyMOL Molecular Graphic system. Results A novel heterozygous nonsense mutation (c.1015 A > T, p.Lys339Ter, p.K339X) within RHO, which cosegregated with retinitis pigmentosa phenotype was detected in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic. Conclusions We identified a novel heterozygous nonsense mutation of RHO gene in a Chinese family with retinitis pigmentosa by target region sequencing and our bioinformatics analysis indicated that the mutation is pathogenic. Our results can broaden the spectrum of RHO gene mutation and enrich the phenotype-genotype correlation of retinitis pigmentosa.

scholarly journals A Novel PRPF31 Mutation in a Large Chinese Family with Autosomal Dominant Retinitis Pigmentosa and Macular Degeneration

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78274 ◽  
Author(s):  
Fang Lu ◽  
Lulin Huang ◽  
Chuntao Lei ◽  
Guiquan Sha ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Macular Degeneration ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Autosomal Dominant Retinitis Pigmentosa

Clinical and Genetic Identification of a Large Chinese Family with Autosomal Dominant Retinitis Pigmentosa

2013 ◽  
Vol 36 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Yezhen Yang ◽  
Di Tian ◽  
Janet Lee ◽  
Jing Zeng ◽  
Huiming Zhang ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Genetic Identification ◽  
Chinese Family ◽  
Autosomal Dominant Retinitis Pigmentosa

Mutations in the Gene Coding for the Pre-mRNA Splicing Factor,PRPF31, in Patients with Autosomal Dominant Retinitis Pigmentosa

2007 ◽  
Vol 48 (3) ◽  
pp. 1330 ◽  
Author(s):  
Naushin H. Waseem ◽  
Veronika Vaclavik ◽  
Andrew Webster ◽  
Sharon A. Jenkins ◽  
Alan C. Bird ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Gene Coding

Mutations in the Pre-mRNA Splicing-Factor GenesPRPF3,PRPF8, andPRPF31in Spanish Families with Autosomal Dominant Retinitis Pigmentosa

2003 ◽  
Vol 44 (5) ◽  
pp. 2171 ◽  
Author(s):  
Mari´a Marti´nez-Gimeno ◽  
Mari´a Jose´ Gamundi ◽  
Imma Hernan ◽  
Miquel Maseras ◽  
Elena Milla´ ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Autosomal Dominant Retinitis Pigmentosa

Gene of the month:PRPF31

2017 ◽  
Vol 70 (9) ◽  
pp. 729-732 ◽  
Author(s):  
Anna M Rose ◽  
Rong Luo ◽  
Utsav K Radia ◽  
Shomi S Bhattacharya
Keyword(s):  
Protein Structure ◽  
Retinitis Pigmentosa ◽  
Visual Impairment ◽  
Retinal Degeneration ◽  
Autosomal Dominant ◽  
Biological Function ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Eukaryotic Cells ◽  
Autosomal Dominant Retinitis Pigmentosa

Pre-mRNA splicing is an essential process in eukaryotic cells where the transcribed intronic sequences are removed, prior to translation into protein. PRPF31 is a ubiquitously expressed splicing factor, which aids in the assembly of the macromolecular spliceosome. Mutations inPRPF31cause autosomal dominant retinitis pigmentosa (adRP), a form of retinal degeneration that causes progressive visual impairment. Interestingly, mutations inPRPF31are non-penetrant, with some mutation carriers being phenotypically unaffected. In this review, the gene organisation, protein structure and biological function of PRPF31 are discussed, and the mechanisms of non-penetrance inPRPF31-associated adRP are discussed.

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