Uncovering the genetic architecture of inherited retinal disease in a consanguineous Iranian cohort
An integrated approach combining whole exome sequencing (WES) and autozygosity mapping was used to molecularly diagnose inherited retinal disease (IRD) in 192 unrelated Iranian families, 76.1% of which originate from a consanguineous background. Data analysis was performed using an in-house pipeline to detect single-nucleotide variants (SNVs), small insertions and deletions, copy number variants (CNVs) and runs of homozygosity (ROHs). Using this approach, we obtained a molecular diagnosis for 72.9% of the cohort. In total, 209 variants were identified in 78 IRD-associated genes. The majority occurred only once (81.8%) and 52.9% were novel. Variants in ROHs were found in 82.8% of patients from consanguineous backgrounds. The importance of structural variation (SV) was demonstrated, with CNVs identified in 5.3%, including several novel CNVs. Multilocus genomic variation was observed in two families. This integrated study using WES and in-depth variant assessment significantly expanded the molecular spectrum of IRD in Iran, an understudied population.
Authors
- Hamid Ahmadieh (ORCID: https://orcid.org/0000-0002-8139-2661)
- Marta Del Pozo‐Valero (ORCID: https://orcid.org/0000-0003-3934-0873)
- Mattias Van Heetvelde (ORCID: https://orcid.org/0000-0001-5758-0366)
- Narsis Daftarian (ORCID: https://orcid.org/0000-0001-5846-8739)
- Toon Rosseel (ORCID: https://orcid.org/0000-0002-8155-3197)
- Miriam Bauwens (ORCID: https://orcid.org/0000-0003-0402-9006)
- Julie De Zaeytijd (ORCID: https://orcid.org/0000-0003-4035-6389)
- Afrooz Moghaddasi
- Mohammadreza Dehghani (ORCID: https://orcid.org/0000-0002-8392-8175)
- Fatemeh Suri (ORCID: https://orcid.org/0000-0002-3170-2940)
- Ebrahim Mohammed Al-Hajj (ORCID: https://orcid.org/0000-0002-5887-1357)
- Tahmineh Motevasseli (ORCID: https://orcid.org/0000-0001-7969-0187)
- Elfride De Baere (ORCID: https://orcid.org/0000-0002-5609-6895)
- Hamideh Sabbaghi (ORCID: https://orcid.org/0000-0002-2627-7222)
- Kristof Van Schil (ORCID: https://orcid.org/0000-0001-5299-8851)
- Marieke De Bruyne (ORCID: https://orcid.org/0000-0001-6636-5537)
- Reza Maroofian (ORCID: https://orcid.org/0000-0001-6763-1542)
- Mohammad Yahya Vahidi Mehrjardi (ORCID: https://orcid.org/0000-0003-0535-1590)
- Quinten Mahieu (ORCID: https://orcid.org/0000-0002-0850-1745)
- Lieselot Vincke
- Leila Javanparast Sheykhani
Institutions
- Shahid Sadoughi University of Medical Sciences and Health Services (IR)
- Ghent University Hospital (BE)
- Antwerp University Hospital (BE)
- Research Institute for Endocrine Sciences (IR)
- Diabetes Research Center
- University College London (GB)
- Shahid Beheshti University of Medical Sciences (IR)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s41525-025-00473-9
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Shahid Beheshti University of Medical Sciences
- Vlaamse regering
- Bijzonder Onderzoeksfonds UGent