Novel and Recurrent Copy Number Variants in -Associated Retinopathy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892127

Authors

Zelia Corradi

Claire-Marie Dhaenens

Olivier Grunewald

Ipek Selen Kocabas

Isabelle Meunier

Sandro Banfi

Marianthi Karali

Frans P M Cremers

Rebekkah J Hitti-Malin

Affiliations

Soon will be listed here.

Abstract

is the most frequently mutated gene leading to inherited retinal disease (IRD) with over 2200 pathogenic variants reported to date. Of these, ~1% are copy number variants (CNVs) involving the deletion or duplication of genomic regions, typically >50 nucleotides in length. An in-depth assessment of the current literature based on the public database LOVD, regarding the presence of known CNVs and structural variants in , and additional sequencing analysis of using single-molecule Molecular Inversion Probes (smMIPs) for 148 probands highlighted recurrent and novel CNVs associated with -associated retinopathies. An analysis of the coverage depth in the sequencing data led to the identification of eleven deletions (six novel and five recurrent), three duplications (one novel and two recurrent) and one complex CNV. Of particular interest was the identification of a complex defect, i.e., a 15.3 kb duplicated segment encompassing exon 31 through intron 41 that was inserted at the junction of a downstream 2.7 kb deletion encompassing intron 44 through intron 47. In addition, we identified a 7.0 kb tandem duplication of intron 1 in three cases. The identification of CNVs in can provide patients and their families with a genetic diagnosis whilst expanding our understanding of the complexity of diseases caused by variants.

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