Genotype Profile of Global EYS-Associated Inherited Retinal Dystrophy and Clinical Findings in a Large Chinese Cohort

PurposeThe aim of this study was to probe the global profile of the EYS-associated genotype-phenotype trait in the worldwide reported IRD cases and to build a model for predicting disease progression as a reference for clinical consultation.MethodsThis retrospective study of 420 well-documented IRD cases with mutations in the EYS gene included 39 patients from a genotype-phenotype study of inherited retinal dystrophy (IRD) conducted at the Beijing Institute of Ophthalmology and 381 cases retrieved from global reports. All patients underwent ophthalmic evaluation. Mutations were revealed using next-generation sequencing, followed by Sanger DNA sequencing and real-time quantitative PCR analysis. Multiple regression models and statistical analysis were used to assess the genotype and phenotype characteristics and traits in this large cohort.ResultsA total of 420 well-defined patients with 841 identified mutations in the EYS gene were successfully obtained. The most common pathogenic variant was a frameshift c.4957dupA (p.S1653Kfs∗2) in exon 26, with an allele frequency of 12.7% (107/841), followed by c.8805C > A (p.Y2935X) in exon 43, with an allele frequency of 5.9% (50/841). Two new hot spots were identified in the Chinese cohort, c.1750G > T (p.E584X) and c.7492G > C (p.A2498P). Several EYS mutation types were identified, with CNV being relatively common. The mean age of onset was 20.54 ± 11.33 (4–46) years. Clinical examinations revealed a typical progression of RPE atrophy from the peripheral area to the macula.ConclusionThis large global cohort of 420 IRD cases, with 262 distinct variants, identified genotype-phenotype correlations and mutation spectra with hotspots in the EYS gene.

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Innate and Autoimmunity in the Pathogenesis of Inherited Retinal Dystrophy

Cells ◽

10.3390/cells9030630 ◽

2020 ◽

Vol 9 (3) ◽

pp. 630 ◽

Cited By ~ 2

Author(s):

T. J. Hollingsworth ◽

Alecia K. Gross

Keyword(s):

Disease Progression ◽

Age Of Onset ◽

Retinal Dystrophy ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies ◽

Major Player ◽

Inherited Retinal Dystrophy ◽

Rate Of Progression ◽

Immunohistochemical Methods ◽

Onset Rate

Inherited retinal dystrophies (RDs) are heterogenous in many aspects including genes involved, age of onset, rate of progression, and treatments. While RDs are caused by a plethora of different mutations, all result in the same outcome of blindness. While treatments, both gene therapy-based and drug-based, have been developed to slow or halt disease progression and prevent further blindness, only a small handful of the forms of RDs have treatments available, which are primarily for recessively inherited forms. Using immunohistochemical methods coupled with electroretinography, optical coherence tomography, and fluorescein angiography, we show that in rhodopsin mutant mice, the involvement of both the innate and the autoimmune systems could be a strong contributing factor in disease progression and pathogenesis. Herein, we show that monocytic phagocytosis and inflammatory cytokine release along with protein citrullination, a major player in forms of autoimmunity, work to enhance the progression of RD associated with a rhodopsin mutation.

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Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-314281 ◽

2019 ◽

Vol 104 (7) ◽

pp. 932-937 ◽

Cited By ~ 3

Author(s):

Ke Xu ◽

Yue Xie ◽

Tengyang Sun ◽

Xiaohui Zhang ◽

Chunjie Chen ◽

...

Keyword(s):

Early Onset ◽

Retinal Dystrophy ◽

Case Series ◽

Clinical Findings ◽

Chinese Patients ◽

Pcr Analysis ◽

Common Mutation ◽

Essential Information ◽

Leber Congenital Amaurosis ◽

Targeted Next Generation Sequencing

BackgroundLeber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD) are clinically and genetically heterogeneous inherited retinal disorders that cause severe visual impairment in children. The objective of this study was to describe the mutation profile and phenotypic characteristics in Chinese patients with LCA or EOSRD.MethodsRetrospective consecutive case series (2010–2017) study was performed in 148 probands (91 with LCA and 57 with EOSRD). All patients underwent ophthalmic evaluation. Mutations were revealed using targeted next-generation sequencing, followed by Sanger DNA-sequencing and real-time quantitative PCR analysis.ResultsWe identified two diseasing-causing mutations in 88 unrelated patients, heterozygous autosomal dominant mutations in 11 probands and X-linked hemizygous mutations in 11 patients, for an overall mutation detection rate of 74.3% (110/148). We detected 158 different disease-causing mutations involving 14 LCA genes, 16 retinitis pigmentosa or cone-rod dystrophy genes and 3 syndromic retinal dystrophy genes. Of these 158 mutations, 98 were novel. The most common mutation was p.Q141X of AIPL1, with a gene-specific allele frequency of 60%. The first five most frequently mutated genes were AIPL1 (11.0%), RPGRIP1 (8.8%) and CEP290, GUCY2D and RPE65 (each 7.7%) in the patients with LCA and RPGR (12.3%), CRB1 (10.5%), RPE65 (10.5%), RDH12 (7.0%) and RP2 (5.3%) in the patients with EOSRD.ConclusionsOur results revealed that the mutation spectrum of patients with LCA differs from that of the patients with EOSRD and established the configuration of the mutation frequencies for each LCA gene in Chinese patients, thereby providing essential information for future genetic counselling and gene therapy.

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Genetic and Phenotypic Landscape of PRPH2-Associated Retinal Dystrophy in Japan

Genes ◽

10.3390/genes12111817 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1817

Author(s):

Akio Oishi ◽

Kaoru Fujinami ◽

Go Mawatari ◽

Nobuhisa Naoi ◽

Yasuhiro Ikeda ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Age Of Onset ◽

Phenotypic Variability ◽

Retinal Dystrophy ◽

Japanese Patients ◽

Macular Dystrophy ◽

Hand Motion ◽

Pathogenic Variants ◽

Inherited Retinal Dystrophy ◽

Asian Cohort

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort.

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Biodegradation of Chloroxylenol by Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373: Insight into Ecotoxicity and Metabolic Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms22094360 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4360

Author(s):

Marta Nowak ◽

Katarzyna Zawadzka ◽

Janusz Szemraj ◽

Aleksandra Góralczyk-Bińkowska ◽

Katarzyna Lisowska

Keyword(s):

Trametes Versicolor ◽

Significant Rise ◽

Pcr Analysis ◽

Cunninghamella Elegans ◽

Oxidation Reactions ◽

Cytochrome P450 Enzymes ◽

C Elegans ◽

Real Time Quantitative Pcr ◽

Genes Expression ◽

By Products

Chloroxylenol (PCMX) is applied as a preservative and disinfectant in personal care products, currently recommended for use to inactivate the SARS-CoV-2 virus. Its intensive application leads to the release of PCMX into the environment, which can have a harmful impact on aquatic and soil biotas. The aim of this study was to assess the mechanism of chloroxylenol biodegradation by the fungal strains Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373, and investigate the ecotoxicity of emerging by-products. The residues of PCMX and formed metabolites were analysed using GC-MS. The elimination of PCMX in the cultures of tested microorganisms was above 70%. Five fungal by-products were detected for the first time. Identified intermediates were performed by dechlorination, hydroxylation, and oxidation reactions catalysed by cytochrome P450 enzymes and laccase. A real-time quantitative PCR analysis confirmed an increase in CYP450 genes expression in C. elegans cells. In the case of T. versicolor, spectrophotometric measurement of the oxidation of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) showed a significant rise in laccase activity during PCMX elimination. Furthermore, with the use of bioindicators from different ecosystems (Daphtoxkit F and Phytotoxkit), it was revealed that the biodegradation process of PCMX had a detoxifying nature.

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Na-K-activated adenosinetriphosphatase in retinae of rats with and without inherited retinal dystrophy

Vision Research ◽

10.1016/0042-6989(70)90124-0 ◽

1970 ◽

Vol 10 (5) ◽

pp. 435-438 ◽

Cited By ~ 10

Author(s):

F.J.M. Daemen ◽

J.J.H.H.M. de Pont ◽

F. Lion ◽

S.L. Bonting

Keyword(s):

Retinal Dystrophy ◽

Inherited Retinal Dystrophy

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Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations

Blood ◽

10.1182/blood-2004-03-1134 ◽

2004 ◽

Vol 104 (9) ◽

pp. 2926-2932 ◽

Cited By ~ 166

Author(s):

S. Branford

Keyword(s):

Real Time ◽

Quantitative Pcr ◽

Kinase Domain ◽

Pcr Analysis ◽

Real Time Quantitative Pcr ◽

Abl Kinase ◽

Kinase Domain Mutations

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Validation of reference genes for reverse transcription real-time quantitative PCR analysis in the deep-sea bacterium Shewanella psychrophila WP2

FEMS Microbiology Letters ◽

10.1093/femsle/fny229 ◽

2018 ◽

Vol 365 (21) ◽

Cited By ~ 3

Author(s):

Shunzhang Liu ◽

Canxing Meng ◽

Guanpeng Xu ◽

Huahua Jian ◽

Fengping Wang

Keyword(s):

Real Time ◽

Quantitative Pcr ◽

Reverse Transcription ◽

Deep Sea ◽

Reference Genes ◽

Pcr Analysis ◽

Real Time Quantitative Pcr

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Study on the expression of specific chimeric-orfs of C type cytoplasmic male sterile in maize

Israel Journal of Plant Sciences ◽

10.1080/07929978.2014.945314 ◽

2013 ◽

Vol 61 (1-4) ◽

pp. 25-36 ◽

Cited By ~ 1

Author(s):

Jiyue Wang ◽

Lihua Zeng ◽

Shengqing Wang ◽

Jing Wang ◽

Yanli Lu ◽

...

Keyword(s):

Base Substitution ◽

Pcr Analysis ◽

Male Sterile ◽

Maintainer Line ◽

Cytoplasmic Male Sterile ◽

Real Time Quantitative Pcr ◽

Substitution Mutations ◽

Membrane Spanning ◽

Insertion Mutations ◽

Online Software

In the present study, a mutated chimericorf364, namedorf366-c, was identified in a maize C type cytoplasmic male sterile line (CMS-C) by PCR and RT-PCR. Four base pair adjacent base substitution mutations (CAAA to TTTT) and eight bp insertion mutations were found inorf366-ccompared withorf364. ORF366-C was predicted to contain one membrane-spanning domain using TMHMM online software. Real-time quantitative PCR analysis showed thatorf366-cwas upregulated in the CMS-C line in comparison to its maintainer line at the uninucleate stage. The protokaryotic protein expression oforf366-cinEscherichia colishowed that ORF366-C could be a cytotoxic protein. All the results indicated thatorf366-cmay be associated with maize CMS-C.

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