Couple-Based Carrier Screening: How Gene and Variant Considerations Impact Outcomes

Area of Science:

• Reproductive genetics
• Clinical diagnostics
• Genomic medicine

Background:

• Clinical utility of reproductive carrier screening is gene-dependent.
• Variant reporting and patient population influence screening outcomes.
• Routine clinical setting evaluation of carrier screening is needed.

Purpose of the Study:

• Evaluate carrier screening outcomes in reproductive couples.
• Assess the clinical utility of couple-based screening.
• Analyze the impact of gene panels and variant reporting.

Main Methods:

• 1595 couples underwent couple-based carrier screening across 390 genes.
• Carrier status assessed on a couple basis; reporting focused on at-risk offspring.
• Conditions classified by severity and variant-specific clinical impact; secondary findings evaluated.

Main Results:

• 4.2% of couples were at risk for a genetic condition.
• 1.0% of couples had high-clinical-impact results, with CFTR, SMN1, or FMR1 involved in 44%.
• 1.7% of individuals had secondary findings with personal utility.

Conclusions:

• Targeted screening of only CFTR, SMN1, and FMR1 misses over half of at-risk couples.
• Couple-based reporting and variant analysis enhance prediction of clinical impact.
• Secondary findings are common, necessitating pre-test counseling.