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Genotype-phenotype correlations
Original research
Whole exome sequencing of 491 individuals with inherited retinal diseases reveals a large spectrum of variants and identification of novel candidate genes
  1. Tamar Hayman1,
  2. Talya Millo1,
  3. Karen Hendler1,
  4. Itay Chowers1,
  5. Menachem Gross2,
  6. Eyal Banin1,
  7. Dror Sharon1
  1. 1Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
  2. 2Otolaryngology/Head and Neck Surgery, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  1. Correspondence to Professor Dror Sharon, Ophthalmology, Hadassah Medical Center, Jerusalem 9190501, Israel; dror.sharon1{at}mail.huji.ac.il

Abstract

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
  • genetics
  • genomics
  • 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.

http://dx.doi.org/10.1136/jmg-2023-109482

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    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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    Footnotes

    • 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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.