Determinants of diagnostic yield in a multi-ethnic Asian inherited retinal disease cohort
As the discovery of new genes causing inherited retinal disease (IRD) has plateaued, we look to other factors which could be used to maximize diagnostic yield. We analyzed whole-exome sequencing (WES) data from 506 IRD probands, focusing on the interplay between diagnostic yield, age of symptom onset or diagnosis, family history, and initial clinical diagnosis. The cohort's overall diagnostic yield was 49.2%. Diagnostic yield was negatively correlated with the age of symptom onset and positively correlated with the number of affected family members. Diseases with distinctive clinical presentations such as Bietti crystalline dystrophy (BCD) or Leber congenital amaurosis (LCA) were more reliably diagnosed than more common and heterogeneous diseases like retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). Recurrent genes and variants in this Chinese-majority cohort resemble those found in Chinese cohort studies but differ from populations of European descent, with implications for the design and prioritization of gene therapies. These insights may help optimize the diagnostic utility of genetic testing for IRDs, enhance the delivery of genetic counseling for patients, and guide the development of more inclusive targeted therapies.
Authors
- Patrick Tan (ORCID: https://orcid.org/0000-0002-0179-8048)
- Yasmin M. Bylstra (ORCID: https://orcid.org/0000-0002-6420-2272)
- Saumya S. Jamuar
- Beau James Fenner (ORCID: https://orcid.org/0000-0002-5356-7604)
- Jane Andrea Lieviant (ORCID: https://orcid.org/0009-0009-5091-6176)
- Tien‐En Tan (ORCID: https://orcid.org/0000-0002-9869-5159)
- Tiffany N. Chao (ORCID: https://orcid.org/0000-0003-1963-0275)
- N. Siew
- Sylvia Kam (ORCID: https://orcid.org/0000-0001-7704-1917)
- Kanika Jain (ORCID: https://orcid.org/0000-0003-1826-4402)
- Jing Xian Teo (ORCID: https://orcid.org/0000-0002-5083-1852)
- Weng Khong Lim (ORCID: https://orcid.org/0000-0003-4391-1130)
- Eranga N. Vithana (ORCID: https://orcid.org/0000-0002-8898-0095)
- Sonia Dávila (ORCID: https://orcid.org/0000-0003-4026-0483)
- Wan Wan Lim
- Choi Mun Chan
- Ranjana Mathur
Institutions
- Agency for Science, Technology and Research (SG)
- SingHealth (SG)
- National University of Singapore (SG)
- Singapore National Eye Center (SG)
- SingHealth Duke-NUS Academic Medical Centre (SG)
- Singapore Institute for Clinical Sciences (SG)
- National University Cancer Institute, Singapore (SG)
- KK Women's and Children's Hospital (SG)
- Singapore Eye Research Institute (SG)
- Duke-NUS Medical School (SG)
- Genome Institute of Singapore (SG)
Publication Details
- Journal
- European Journal of Human Genetics
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1038/s41431-025-01833-w
- Citations
- 8
- Primary Topic
- Retinal Development and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 6.45