scholarly journals Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F ‐mediated inherited retinal disorders

2019 ◽  
Vol 40 (6) ◽  
pp. 765-787 ◽  
Author(s):  
Christina Zeitz ◽  
Christelle Michiels ◽  
Marion Neuillé ◽  
Christoph Friedburg ◽  
Christel Condroyer ◽  
...  
Keyword(s):  
Missing Gene ◽  
Retinal Disorders ◽  
Gene Defects ◽  
Inherited Retinal Disorders

scholarly journals A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1240
Author(s):  
Agnieszka Rafalska ◽  
Anna M. Tracewska ◽  
Anna Turno-Kręcicka ◽  
Milena J. Szafraniec ◽  
Marta Misiuk-Hojło
Keyword(s):  
Vision Loss ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Mild Phenotype ◽  
Cone Function ◽  
Retinal Disorders ◽  
Molecular Inversion Probes ◽  
Disease Experience ◽  
The Individual ◽  
Inherited Retinal Disorders

CEP290 is a ciliary gene frequently mutated in ciliopathies, resulting in a broad range of phenotypes, ranging from isolated inherited retinal disorders (IRDs) to severe or lethal syndromes with multisystemic involvement. Patients with non-syndromic CEP290-linked disease experience profound and early vision loss due to cone-rod dystrophy, as in Leber congenital amaurosis. In this case report, we describe two novel loss-of-function heterozygous alterations in the CEP290 gene, discovered in a patient suffering from retinitis pigmentosa using massive parallel sequencing of a molecular inversion probes library constructed for 108 genes involved in IRDs. A milder phenotype than expected was found in the individual, which serves to prove that some CEP290-associated disorders may display preserved cone function.

Microperimetry in Three Inherited Retinal Disorders

2019 ◽  
Vol 34 (4) ◽  
pp. 334-339 ◽  
Author(s):  
Laura Bagdonaite-Bejarano ◽  
Ronald M. Hansen ◽  
Anne B. Fulton
Keyword(s):  
Retinal Disorders ◽  
Inherited Retinal Disorders

scholarly journals Gene and cell-based therapies for inherited retinal disorders: An update

2016 ◽  
Vol 172 (4) ◽  
pp. 349-366 ◽  
Author(s):  
Jesse D. Sengillo ◽  
Sally Justus ◽  
Yi-Ting Tsai ◽  
Thiago Cabral ◽  
Stephen H. Tsang
Keyword(s):  
Retinal Disorders ◽  
Inherited Retinal Disorders

scholarly journals Novel Homozygous TULP1 and RPE65 Variants Underlies Recessive Retinitis Pigmentosa

2020 ◽  
Author(s):  
Amjad Khan ◽  
Xiao Bai ◽  
Muhammad Umair ◽  
Shirui Han ◽  
Xiaerbati Habulieti ◽  
...  
Keyword(s):  
Data Analysis ◽  
Retinitis Pigmentosa ◽  
Molecular Mechanisms ◽  
Mutation Screening ◽  
Missense Variant ◽  
Disease Phenotype ◽  
Whole Exome ◽  
Retinal Disorders ◽  
Pakistani Families ◽  
Inherited Retinal Disorders

Retinitis pigmentosa (RP) clinically and genetically heterogeneous group of inherited retinal disorders (IRD) that result in retinal degeneration. This study aimed to identify the genetic findings of patients with autosomal recessive retinitis pigmentosa (arRP). Whole exome sequencing (WES) was performed in two unrelated Pakistani families underlying arRP. Data analysis and mutation screening was performed for all the known RP genes following bi-directional Sanger sequencing to determine whether any of the candidate variants co-segregated with the disease phenotype in the families. WES data analysis revealed a novel homozygous missense variant (c.1274T>C) in the in Tubby like Protein 1 (TULP1 NM_003322.6) gene in family 1 and a novel homozygous frameshift variant (c.351delC) in the retinoid isomerohydrolase 65 (RPE65 NM_000329.3) gene in family 2. The identified variants perfectly co-segregated with the disease phenotype within the families. Our results strongly suggest that mutations in TULP1 and RPE65 are responsible for the retinal phenotype in the affected individuals. These mutations will increase the mutation spectrum of these genes; furthermore, it will enhance our knowledge and understanding of the underlying molecular mechanisms of retinitis pigmentosa.

scholarly journals Care Pathway of RPE65-Related Inherited Retinal Disorders from Early Symptoms to Genetic Counseling: A Multicenter Narrative Medicine Project in Italy

2021 ◽  
Vol Volume 15 ◽  
pp. 4591-4605
Author(s):  
Francesca Simonelli ◽  
Andrea Sodi ◽  
Benedetto Falsini ◽  
Giacomo Bacci ◽  
Giancarlo Iarossi ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Care Pathway ◽  
Narrative Medicine ◽  
Early Symptoms ◽  
Retinal Disorders ◽  
Inherited Retinal Disorders

Gene Therapy for Inherited Retinal Disorders: Update on Clinical Trials

2021 ◽  
Vol 238 (03) ◽  
pp. 272-281
Author(s):  
Stylianos Michalakis ◽  
Maximilian Gerhardt ◽  
Günter Rudolph ◽  
Siegfried Priglinger ◽  
Claudia Priglinger
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Product ◽  
Autosomal Dominant ◽  
Retinal Dystrophy ◽  
Adeno Associated Virus ◽  
Retinal Disorders ◽  
Alternative Approaches ◽  
Or Gene ◽  
Inherited Retinal Disorders

AbstractWithin the last decade, continuous advances in molecular biological techniques have made it possible to develop causative therapies for inherited retinal disorders (IRDs). Some of the most promising options are gene-specific approaches using adeno-associated virus-based vectors to express a healthy copy of the disease-causing gene in affected cells of a patient. This concept of gene supplementation therapy is already advocated for the treatment of retinal dystrophy in RPE65-linked Leberʼs congenital amaurosis (LCA) patients. While the concept of gene supplementation therapy can be applied to treat autosomal recessive and X-linked forms of IRD, it is not sufficient for autosomal dominant IRDs, where the pathogenic gene product needs to be removed. Therefore, for autosomal dominant IRDs, alternative approaches that utilize CRISPR/Cas9 or antisense oligonucleotides to edit or deplete the mutant allele or gene product are needed. In recent years, research retinal gene therapy has intensified and promising approaches for various forms of IRD are currently in preclinical and clinical development. This review article provides an overview of current clinical trials for the treatment of IRDs.

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