Article
Medicine, General & Internal
Tao Zhang, Jingshan Bai, Xinyi Zhang, Xiaowei Zheng, Nan Lu, Zhongyin Liang, Ling Lin, Yongsong Chen
Summary: This study identified a novel heterozygous SNRNP200(c.C6088T) mutation that causes retinitis pigmentosa through a dominant-negative effect.
FRONTIERS IN MEDICINE
(2021)
Article
Genetics & Heredity
Brian G. Ballios, Emily M. Place, Luis Martinez-Velazquez, Eric A. Pierce, Jason I. Comander, Rachel M. Huckfeldt
Summary: Sector and pericentral forms of hereditary retinitis pigmentosa are rare, and studies suggest that they may have distinct disease spectra. Analysis of a specific genotype revealed a wide phenotypic range in patients, with significant intrafamilial variability in phenotype. Long-term follow-up showed good prognosis for central visual acuity in the absence of macular disease, but disease progression over extended periods was observed.
Article
Medicine, General & Internal
Yuanzheng Lan, Yuhong Chen, Yunsheng Qiao, Qingdan Xu, Ruyi Zhai, Xinghuai Sun, Jihong Wu, Xueli Chen
Summary: This study aimed to identify the genetic cause of autosomal dominant retinitis pigmentosa (adRP) in a Chinese family and investigate the molecular mechanisms of incomplete penetrance. Through whole-genome sequencing and RNA-seq analysis, a novel large deletion of a gene was identified in mutation carriers, leading to significant differential gene expression compared to healthy controls.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Dongju Won, Joo-Yeon Hwang, Yeeun Shim, Suk Ho Byeon, Junwon Lee, Christopher Seungkyu Lee, Min Kim, Hyun Taek Lim, Jong Rak Choi, Seung-Tae Lee, Jinu Han
Summary: MEIs are often missed due to exceeding read lengths of short-read sequencing technologies, but a grep search program was developed in this study to efficiently detect the RP1 Alu insertion. The Alu insertion in RP1 exon 4 was found to be a common founder mutation in Korean population.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Ting Xiao, Yue Xie, Xin Zhang, Ke Xu, Xiaohui Zhang, Zi-Bing Jin, Yang Li
Summary: By studying the variant spectrum of related genes in Chinese patients with retinitis pigmentosa, multiple genetic variants associated with the disease were identified, providing important information for genetic counseling and disease treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Ophthalmology
Wei Liu, Ruru Guo, Huijie Hao, Jian Ji
Summary: A novel heterozygous nonsense mutation of RHO gene was identified in a Chinese family with retinitis pigmentosa through targeted region sequencing. Bioinformatics analysis indicated that the mutation is pathogenic, expanding the spectrum of RHO gene mutations and enriching the phenotype-genotype correlation of retinitis pigmentosa.
Article
Biochemistry & Molecular Biology
Roslin J. Adamson, N. Connor Payne, Sergio G. Bartual, Ralph Mazitschek, Alex N. Bullock
Summary: KEAP1 promotes the ubiquitin-dependent degradation of NRF2 by assembling into a CUL3-dependent ubiquitin ligase complex. Oxidative and electrophilic stress inhibit KEAP1, allowing NRF2 to accumulate for stress response gene transactivation. The crystal structure of the BTB and 3-box domains of human KEAP1 in complex with the CUL3 N-terminal domain revealed a heterotetrameric assembly with 2:2 stoichiometry. The developed TRFRET-based assay system and binding profile data provide valuable insights into the KEAP1-CUL3 interaction.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Ophthalmology
Grant A. A. Justin, Aniz Girach, Ramiro S. S. Maldonado
Summary: This review discusses the use of antisense oligonucleotide (ASON) therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the P23H mutation. Recent findings show that viral and nonviral therapies are being investigated, with ASONs showing promising results in animal models and undergoing a phase 1/2 clinical trial in humans. ASON therapy does not require the use of a viral vector, is delivered through intravitreal injection, and its effects are reversible.
CURRENT OPINION IN OPHTHALMOLOGY
(2023)
Article
Medicine, Research & Experimental
Wei Du, Jiarui Li, Xin Tang, Wenzhen Yu, Mingwei Zhao
Summary: In this study, a CRISPR/SaCas9-mediated gene reduction system was developed to inactivate Rho gene mutation and replace normal rhodopsin in a specific mouse model, leading to improved retinal function. These findings suggest that CRISPR/SaCas9-based reduction and replacement gene therapy could potentially offer therapeutic benefits for Rho mutant ADRP.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Ophthalmology
Junwen Wang, Yingwei Wang, Yi Jiang, Xueqing Li, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Wenmin Sun, Panfeng Wang, Qingjiong Zhang
Summary: This study found that truncating variants of TOPORS are clustered in specific residues, while variants outside this region and CNVs involving the N-terminus are not associated with RP. These findings provide valuable information for interpreting variation in TOPORS and other genes in similar situations, especially for CNVs.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Ophthalmology
Veronika Vaclavik, Leila Tiab, Young Joo Sun, Vinit B. Mahajan, Alexandre Moulin, Nathalie Allaman-Pillet, Francis L. Munier, Daniel F. Schorderet
Summary: Variants in the gene COL6A6 on chromosome 3p22.1 are linked to retinitis pigmentosa (RP) with autosomal dominant transmission. This form of RP is characterized by late-onset rod cone dystrophy with retained visual acuity and mild progression, suggesting important implications for patient counseling.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Neurosciences
Chulbul M. Ahmeda, Michael T. Massengill, Cristhian J. Ildefonso, Archana Jalligampala, Ping Zhu, Hung Li, Anil P. Patel, Maureen A. McCall, Alfred S. Lewin
Summary: This study found that AAV-RHO820-shRNA820 can slow the loss of photoreceptor cells and preserve retinal function in P23H RHO transgenic mice. Moreover, the untreated contralateral eyes also showed the same protective effect. This suggests that RNA replacement therapy may provide clinical benefit to both eyes of adRP patients.
Article
Ophthalmology
Junxing Yang, Xueshan Xiao, Wenmin Sun, Shiqiang Li, Xiaoyun Jia, Qingjiong Zhang
Summary: This study aimed to verify the correlation between RCBTB1 variations and phenotypes by analyzing genetic data from a large number of families. The findings suggest that truncation variants in the RCBTB1 gene are associated with autosomal recessive RP, rather than with FEVR.
CURRENT EYE RESEARCH
(2021)
Article
Cell & Tissue Engineering
Hajrah Sarkar, Cecile Mejecase, Philippa Harding, Jonathan Eintracht, Lyes Toualbi, Dulce Lima Cunha, Mariya Moosajee
Summary: Induced pluripotent stem cell (iPSC) lines were successfully generated from two patients with different RDH12 variants, expressing pluripotency markers and exhibiting differentiation potential. These cell lines will be used for disease modeling, comparison of disease mechanisms, identification of therapeutic targets, and drug screening.
STEM CELL RESEARCH
(2021)
Article
Genetics & Heredity
Mbarka Bchetnia, Rebecca Dionne Gagne, Julie Powell, Charles Morin, Catherine McCuaig, Audrey Duperee, Lucie Germain, Jacques P. Tremblay, Catherine Laprise
Summary: This study aimed to treat EBS by gene disruption and successfully achieved specific inactivation of the mutant allele in patient's keratinocytes. The edited EBS patient keratinocytes produced lower levels of proteins without any disturbance to cellular properties.