Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2017 Nov 4

PMID 29099798

Citations 31

Authors

Adrian Dockery

Kirk Stephenson

David Keegan

Niamh Wynne

Giuliana Silvestri

Peter Humphries

Paul F Kenna

Matthew Carrigan

G Jane Farrar

Affiliations

Soon will be listed here.

Abstract

There are an estimated 5000 people in Ireland who currently have an inherited retinal degeneration (IRD). It is the goal of this study, through genetic diagnosis, to better enable these 5000 individuals to obtain a clearer understanding of their condition and improved access to potentially applicable therapies. Here we show the current findings of a target capture next-generation sequencing study of over 750 patients from over 520 pedigrees currently situated in Ireland. We also demonstrate how processes can be implemented to retrospectively analyse patient datasets for the detection of structural variants in previously obtained sequencing reads. Pathogenic or likely pathogenic mutations were detected in 68% of pedigrees tested. We report nearly 30 novel mutations including three large structural variants. The population statistics related to our findings are presented by condition and credited to their respective candidate gene mutations. Rediagnosis rates of clinical phenotypes after genotyping are discussed. Possible causes of failure to detect a candidate mutation are evaluated. Future elements of this project, with a specific emphasis on structural variants and non-coding pathogenic variants, are expected to increase detection rates further and thereby produce an even more comprehensive representation of the genetic landscape of IRDs in Ireland.

Citing Articles

Expanding the Mutation Spectrum for Inherited Retinal Diseases.

Lynn J, Huang S, Trigler G, Kingsley R, Coussa R, Bennett L Genes (Basel). 2025; 16(1).

PMID: 39858579 PMC: 11764958. DOI: 10.3390/genes16010032.

Novel Splice-Altering Variants in the and Genes Causative of X-Linked Choroideremia and Cone Dystrophy.

Ridgeway A, Shortall C, Finnegan L, Long R, Matthews E, Dockery A Genes (Basel). 2025; 16(1).

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Phenotypic and Genetic Spectrum in 309 Consecutive Pediatric Patients with Inherited Retinal Disease.

Priglinger C, Gerhardt M, Priglinger S, Schaumberger M, Neuhann T, Bolz H Int J Mol Sci. 2024; 25(22).

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Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4.

Suarez-Herrera N, Riswick I, Vazquez-Dominguez I, Duijkers L, Karjosukarso D, Piccolo D Mol Ther. 2024; 32(3):837-851.

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Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases.

Weisschuh N, Mazzola P, Zuleger T, Schaeferhoff K, Kuhlewein L, Kortum F J Med Genet. 2023; 61(2):186-195.

PMID: 37734845 PMC: 10850689. DOI: 10.1136/jmg-2023-109470.

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