Objective:
To estimate the population-level penetrance of Mendelian variants associated with inherited retinal diseases (IRDs) and understand its implications for genetic testing and disease management.
Approach:
- Only 9% to 28% of individuals with IRD-associated genotypes showed evidence of retinal disease, highlighting a significant gap in clinical diagnosis.
- The most common genes associated with IRD-compatible genotypes included PRPH2, CRX, RHO, RPGR, BEST1, and RP1, which have implications for genetic counseling.
- The DAF ranged from 9.4% for IRD-specific codes to 28.1% for broader screening codes, indicating variability in disease recognition.
- Among UK Biobank participants, 16.1% had definite IRD-compatible abnormalities, rising to 27.9% with less definitive cases, suggesting a need for improved diagnostic criteria.
- Potential biobank recruitment bias may have affected penetrance estimates, particularly in underrepresented populations.
- UK Biobank imaging data is limited, possibly missing early IRD manifestations, especially in the retinal periphery.
- Age differences between study populations could impact penetrance generalizability, particularly for late-onset IRDs.
Key Findings:
Interpretation:
The findings indicate that IRD-associated variants often exhibit incomplete penetrance, suggesting that additional genetic or environmental factors may significantly influence disease manifestation and clinical outcomes.
Limitations:
Conclusion:
The study suggests that IRDs result from interactions between rare genetic variants and individual backgrounds, indicating a critical need for further research into modifying factors of penetrance and expressivity to enhance genetic testing and patient management.
Sources:
This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.
