期刊
GENETICS IN MEDICINE
卷 21, 期 9, 页码 1931-1939出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41436-019-0466-5
关键词
genetic testing; expanded carrier screening; clinical utility; clinical guidelines; clinical detection rate
资金
- Myriad Women's Health
Purpose: The American College of Obstetricians and Gynecologists (AGOG) proposed seven criteria for expanded carrier screening (ECS) panel design. To ensure that screening for a condition is sufficiently sensitive to identify carriers and reduce residual risk of noncarriers, one criterion requires a per-condition carrier rate greater than 1 in 100. However, it is unestablished whether this threshold corresponds with a loss in clinical detection. The impact of the proposed panel design criteria on at-risk couple detection warrants data-driven evaluation. Methods: Carrier rates and at-risk couple rates were calculated in 56,281 patients who underwent a 176-condition ECS and were evaluated for panels satisfying various criteria. Condition-specific clinical detection rates were estimated via simulation. Results: Different interpretations of the 1-in-100 criterion have variable impact: a compliant panel would include between 3 and 38 conditions, identify 11-81% fewer at-risk couples, and detect 36-79% fewer carriers than a 176-condition panel. If the carrier rate threshold must be exceeded in all ethnicities, ECS panels would lack prevalent conditions like cystic fibrosis. Simulations suggest that the clinical detection rate remains >84% for conditions with carrier rates as low as 1 in 1000. Conclusion: The 1-in-100 criterion limits at-risk couple detection and should be reconsidered.
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