scholarly journals Identifying Retinal Disease Genes: How Far Have We Come, How Far Do We Have to Go?

2008 ◽  
pp. 17-36 ◽  
Author(s):  
Stephen P. Daiger
Keyword(s):  
Retinal Disease ◽  
Disease Genes

scholarly journals Phenocopy of a heterozygous carrier of X-linked retinitis pigmentosa due to mosaicism for a RHO variant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ine Strubbe ◽  
Caroline Van Cauwenbergh ◽  
Julie De Zaeytijd ◽  
Sarah De Jaegere ◽  
Marieke De Bruyne ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Somatic Mosaicism ◽  
Retinal Disease ◽  
Hair Follicles ◽  
Disease Genes ◽  
Female Carrier ◽  
Autofluorescence Imaging ◽  
Targeted Next Generation Sequencing ◽  
Whole Exome ◽  
Next Generation Sequencing Ngs

AbstractWe describe both phenotype and pathogenesis in two male siblings with typical retinitis pigmentosa (RP) and the potentially X-linked RP (XLRP) carrier phenotype in their mother. Two affected sons, two unaffected daughters, and their mother underwent detailed ophthalmological assessments including Goldmann perimetry, color vision testing, multimodal imaging and ISCEV-standard electroretinography. Genetic testing consisted of targeted next-generation sequencing (NGS) of known XLRP genes and whole exome sequencing (WES) of known inherited retinal disease genes (RetNet-WES). Variant validation and segregation analysis were performed by Sanger sequencing. The mutational load of the RHO variant in the mother was assessed in DNA from leucocytes, buccal cells and hair follicles using targeted NGS. Both affected sons showed signs of classical RP, while the mother displayed patches of hyperautofluorescence on blue light autofluorescence imaging and regional, intraretinal, spicular pigmentation, reminiscent of a carrier phenotype of XLRP. XLRP testing was negative. RetNet-WES testing revealed RHO variant c.404G > C p.(Arg135Pro) in a mosaic state (21% of the reads) in the mother and in a heterozygous state in both sons. Targeted NGQSS of the RHO variant in different maternal tissues showed a mutation load between 25.06% and 41.72%. We report for the first time that somatic mosaicism of RHO variant c.404G > C p.(Arg135Pro) mimics the phenotype of a female carrier of XLRP, in combination with heterozygosity for the variant in the two affected sons.

scholarly journals Characterization of New Transcripts Enriched in the Mouse Retina and Identification of Candidate Retinal Disease Genes

2004 ◽  
Vol 45 (9) ◽  
pp. 3313 ◽  
Author(s):  
Julie Lord-Grignon ◽  
Nicolas Te´treault ◽  
Alan J. Mears ◽  
Anand Swaroop ◽  
Gilbert Bernier
Keyword(s):  
Retinal Disease ◽  
Mouse Retina ◽  
Disease Genes

scholarly journals Comprehensive Analysis of Photoreceptor Gene Expression and the Identification of Candidate Retinal Disease Genes

Cell ◽  
2001 ◽  
Vol 107 (5) ◽  
pp. 579-589 ◽  
Author(s):  
Seth Blackshaw ◽  
Rebecca E. Fraioli ◽  
Takahisa Furukawa ◽  
Constance L. Cepko
Keyword(s):  
Gene Expression ◽  
Retinal Disease ◽  
Comprehensive Analysis ◽  
Disease Genes

scholarly journals AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa

2021 ◽  
Author(s):  
Yunlu Xue ◽  
Sean K. Wang ◽  
Parimal Rana ◽  
Emma R. West ◽  
Christin M. Hong ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Mouse Models ◽  
Retinal Disease ◽  
Disease Genes ◽  
Cone Photoreceptors ◽  
Adeno Associated Virus ◽  
Rescue Effect ◽  
Inherited Retinal Disease ◽  
High Acuity

AbstractRetinitis pigmentosa (RP) is an inherited retinal disease, affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a gene-agnostic therapy, we screened ≈20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus (AAV) vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb), and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.

scholarly journals Prioritization of Retinal Disease Genes: An Integrative Approach

2013 ◽  
Vol 34 (6) ◽  
pp. 853-859 ◽  
Author(s):  
Alex H. Wagner ◽  
Kyle R. Taylor ◽  
Adam P. DeLuca ◽  
Thomas L. Casavant ◽  
Robert F. Mullins ◽  
...  
Keyword(s):  
Retinal Disease ◽  
Integrative Approach ◽  
Disease Genes

scholarly journals Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations

2017 ◽  
Vol 20 (2) ◽  
pp. 202-213 ◽  
Author(s):  
Kristof Van Schil ◽  
◽  
Sarah Naessens ◽  
Stijn Van de Sompele ◽  
Marjolein Carron ◽  
...  
Keyword(s):  
Copy Number ◽  
Retinal Disease ◽  
Copy Number Variations ◽  
Disease Genes ◽  
Inherited Retinal Disease ◽  
Genomic Landscape

scholarly journals Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

2006 ◽  
Vol 47 (6) ◽  
pp. 2305 ◽  
Author(s):  
Catherine Bowes Rickman ◽  
Jessica N. Ebright ◽  
Zachary J. Zavodni ◽  
Ling Yu ◽  
Tianyuan Wang ◽  
...  
Keyword(s):  
Retinal Disease ◽  
Disease Genes

scholarly journals Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile

2019 ◽  
Author(s):  
Panpan Ye ◽  
Jia Xu ◽  
Yueqiu Luo ◽  
Zhitao Su ◽  
ke yao
Keyword(s):  
Missense Mutation ◽  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Subretinal Fluid ◽  
Retinal Disease ◽  
Angle Closure ◽  
Chinese Family ◽  
Disease Genes ◽  
Metabolomic Profile

Abstract BackgroundAutosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB.MethodsOphthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature.ResultsThe affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G>A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid.ConclusionsWe identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB. Our findings helped improve the understanding of ARB mechanisms.

scholarly journals Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration

2020 ◽  
Vol 21 (21) ◽  
pp. 8083
Author(s):  
Ayse M. Genc ◽  
Mustafa S. Makia ◽  
Tirthankar Sinha ◽  
Shannon M. Conley ◽  
Muayyad R. Al-Ubaidi ◽  
...  
Keyword(s):  
Retinal Disease ◽  
Specific Protein ◽  
Protective Role ◽  
Flavin Mononucleotide ◽  
Disease Genes ◽  
Cellular Mechanisms ◽  
Photoreceptor Outer Segment ◽  
Disease Etiology ◽  
Retinal Degenerations ◽  
Metabolic Dysregulation

The large number of inherited retinal disease genes (IRD), including the photopigment rhodopsin and the photoreceptor outer segment (OS) structural component peripherin 2 (PRPH2), has prompted interest in identifying common cellular mechanisms involved in degeneration. Although metabolic dysregulation has been shown to play an important role in the progression of the disease etiology, identifying a common regulator that can preserve the metabolic ecosystem is needed for future development of neuroprotective treatments. Here, we investigated whether retbindin (RTBDN), a rod-specific protein with riboflavin binding capability, and a regulator of riboflavin-derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is protective to the retina in different IRD models; one carrying the P23H mutation in rhodopsin (which causes retinitis pigmentosa) and one carrying the Y141C mutation in Prph2 (which causes a blended cone-rod dystrophy). RTBDN levels are significantly upregulated in both the rhodopsin (Rho)P23H/+ and Prph2Y141C/+ retinas. Rod and cone structural and functional degeneration worsened in models lacking RTBDN. In addition, removing Rtbdn worsened other phenotypes, such as fundus flecking. Retinal flavin levels were reduced in RhoP23H/+/Rtbdn−/− and Prph2Y141C/+/Rtbdn−/− retinas. Overall, these findings suggest that RTBDN may play a protective role during retinal degenerations that occur at varying rates and due to varying disease mechanisms.

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