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- Title
Novel and Recurrent Copy Number Variants in ABCA4 -Associated Retinopathy.
- Authors
Corradi, Zelia; Dhaenens, Claire-Marie; Grunewald, Olivier; Kocabaş, Ipek Selen; Meunier, Isabelle; Banfi, Sandro; Karali, Marianthi; Cremers, Frans P. M.; Hitti-Malin, Rebekkah J.
- Abstract
ABCA4 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 ABCA4, and additional sequencing analysis of ABCA4 using single-molecule Molecular Inversion Probes (smMIPs) for 148 probands highlighted recurrent and novel CNVs associated with ABCA4-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 ABCA4 can provide patients and their families with a genetic diagnosis whilst expanding our understanding of the complexity of diseases caused by ABCA4 variants.
- Subjects
DNA copy number variations; MOLECULAR probes; IDENTIFICATION; RETINAL diseases; GENETIC disorders; GENETIC disorder diagnosis; RECURRENT neural networks
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 11, p5940
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25115940