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  4. Genetics of Retinitis Pigmentosa and Other Hereditary Retinal Disorders in Western Switzerland
 
research article

Genetics of Retinitis Pigmentosa and Other Hereditary Retinal Disorders in Western Switzerland

Conti, Giovanni Marco
•
Vaclavik, Veronika
•
Rivolta, Carlo
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January 1, 2024
Ophthalmic Research

Introduction: Mutational screening of inherited retinal disorders is prerequisite for gene targeted therapy. Our aim was to report and analyze the proportions of mutations in inherited retinal disease (IRD)-causing genes from a single center in Switzerland in order to describe the distribution of IRDs in Western Switzerland. Methods: We conducted a retrospective study of patient records. Criteria for inclusion were residence in Western Switzerland for patients and relatives presenting a clinical diagnosis of IRDs and an established molecular diagnosis managed by the genetics service of the Jules-Gonin Eye Hospital (JGEH) of Lausanne between January 2002 and December 2022. We initially investigated the IRD phenotypes in all patients (full cohort) with a clinical diagnosis, then calculated the distribution of IRD gene mutations in the entire cohort (genetically determined cohort). We analyzed a sub-group that comprised pediatric patients (<= 18 years of age). In addition, we calculated the distribution of gene mutations within the most represented IRDs. Comprehensive gene screening was performed using a combined approach of different generation of DNA microarray analysis, direct sequencing, and Sanger sequencing. Results: The full cohort comprised 899 individuals from 690 families with a clinical diagnosis of IRDs. We identified 400 individuals from 285 families with an elucidated molecular diagnosis (variants in 84 genes) in the genetically determined cohort. The pediatric cohort included 89 individuals from 65 families with an elucidated molecular diagnosis. The molecular diagnosis rate for the genetically determined cohort was 58.2% (family ratio) and the 5 most frequently implicated genes per family were ABCA4 (11.6%), USH2A (7.4%), EYS (6.7%), PRPH2 (6.3%), and BEST1 (4.6%). The pediatric cohort had a family molecular diagnosis rate of 64.4% and the 5 most common mutated genes per family were RS1 (9.2%), ABCA4 (7.7%), CNGB3 (7.7%), CACNA1F (6.2%), CEP290 (4.6%). Conclusions: This study describes the genetic mutation landscape of IRDs in Western Switzerland in order to quantify their disease burden and contribute to a better orientation of the development of future gene targeted therapies.

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Type
research article
DOI
10.1159/000536036
Web of Science ID

WOS:001235671400025

Author(s)
Conti, Giovanni Marco
Vaclavik, Veronika
Rivolta, Carlo
Escher, Pascal
Schorderet, Daniel Francis  
Munier, Francis L.
Tran, Hoai Viet
Date Issued

2024-01-01

Publisher

Karger

Published in
Ophthalmic Research
Volume

67

Issue

1

Start page

172

End page

182

Subjects

Life Sciences & Biomedicine

•

Inherited Retinal Disorder

•

Switzerland

•

Molecular Characterization

•

Genetic Landscape

•

Retinitis Pigmentosa

•

Rod-Cone Dystrophy

•

Macular Dystrophy

•

Cone-Rod Dystrophy

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Choroidal Dystrophy

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Next-Generation Sequencing

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Pediatric Retinal Dystrophy

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
SV  
Available on Infoscience
June 19, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/208696
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