Abstract
PurposeThe American College of Obstetricians and Gynecologists (ACOG) 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. MethodsCarrier 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. ResultsDifferent interpretations of the 1-in-100 criterion have variable impact: a compliant panel would include between 3 and 38 conditions, identify11–81% fewer at-risk couples, and detect 36–79% fewer carriers than a176-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. ConclusionThe 1-in-100 criterion limits at-risk couple detection and should be reconsidered.
Highlights
Carrier screening facilitates reproductive decision-making by identifying couples at risk for conceptuses affected with autosomal recessive (AR) and X-linked conditions.[1]
Simulations suggest that the clinical detection rate remains >84% for conditions with carrier rates as low as 1 in 1000
Instead of a carrier rate threshold, we propose an alternative measure—estimation of a clinical detection rate—to evaluate when a condition is too rare to be included in an expanded carrier screening (ECS) panel by quantifying if there is enough evidence to determine the clinical association between detected variants and disease
Summary
Carrier screening facilitates reproductive decision-making by identifying couples at risk for conceptuses affected with autosomal recessive (AR) and X-linked conditions.[1] Advances in genomic technology coupled with decreasing sequencing costs have led to the advent and adoption of expanded carrier screening (ECS) for tens to hundreds of recessive conditions simultaneously.[2] For AR conditions, a couple is at risk if both individuals are carriers of the same condition, with the conceptus having a 25% probability of being affected with the condition. For X-linked conditions, a couple is at risk if the female is a carrier: the probability of a male conceptus being affected with the condition can be up to 50% No consensus exists on which conditions should be included on an ECS panel
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Genetics in medicine : official journal of the American College of Medical Genetics
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
