Background Inherited retinal diseases (IRDs) include a range of vision loss conditions caused by variants in different genes. The clinical and genetic heterogeneity make identification of the genetic cause challenging. Here, a cohort of 491 unsolved cases from our cohort of Israeli and Palestinian families with IRDs underwent whole exome sequencing (WES), including detection of CNVs as well as single nucleotide variants (SNVs).
Methods All participants underwent clinical examinations. Following WES on DNA samples by 3 billion, initial SNV analysis was performed by 3 billion and SNV and CNV analysis by Franklin Genoox. The CNVs indicated by the programme were confirmed by PCR followed by gel electrophoresis.
Results WES of 491 IRD cases revealed the genetic cause of disease in 51% of cases, of which 11% were due wholly or in part to CNVs. In two cases, we clarified previously incorrect or unclear clinical diagnoses. This analysis also identified ESRRB and DNM1 as potential novel genes.
Conclusion This analysis is the most extensive one to include CNVs to examine IRD causing genes in the Israeli and Palestinian populations. It has allowed us to identify the causative variant of many patients with IRDs including ones with unclear diagnoses and potential novel genes.
- genetic diseases, inborn
- genetic heterogeneity
- genetic testing
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.
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Contributors TH and TM contributed equally to this paper. Conceptualisation: DS, EB. Data curation: TH, TM, KH, IC, MG, EB. Formal analysis: TH, TM, KH, IC, MG, EB. Funding acquisition: DS, EB. Investigation: DS, EB. Methodology: TH, TM. Project administration: DS. Supervision: DS. Validation: TH, DS. Writing of the original draft: TH, DS. Writing of the review and editing: TH, TM, KH, IC, MG, EB, DS. Ethics declaration: DS, EB. Guarantor: DS.
Funding This study was supported by the Israel Science Foundation (grant number 1778/20) within the Israel Precision Medicine Partnership program, the Foundation Fighting Blindness, (grant BR-GE-0214-0734 to DS and EB), the Yedidut Research grant (to EB), and the Israeli Ministry of Health (grant 3-12583 to DS and EB).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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