Technical factors to consider when developing an Expanded Carrier Screening platform.

Area of Science:

• Genetics
• Reproductive Medicine
• Clinical Diagnostics

Background:

• Expanded Carrier Screening (ECS) identifies carriers for numerous autosomal recessive and X-linked disorders.
• Increasing clinical use of ECS highlights ongoing debates regarding technical implementation.

Purpose of the Study:

• To review best practice criteria for enhancing the clinical utility and validity of Expanded Carrier Screening (ECS) panels.
• To address key considerations for optimizing ECS panel content and variant reporting.

Main Methods:

• Literature review of current research on Expanded Carrier Screening (ECS) panel implementation.
• Analysis of criteria for selecting genes and pathologies for ECS panels.
• Discussion of challenges related to Variant of Uncertain Significance (VUS) reporting.

Main Results:

• Optimal ECS panel design requires consideration of disease severity, general population prevalence, and robust gene-disease associations.
• Reporting of Variants of Uncertain Significance (VUS) presents significant clinical challenges.
• Periodic reassessment of ECS panels is necessary to maintain clinical relevance.

Conclusions:

• Implementing standardized criteria can improve the clinical utility and validity of Expanded Carrier Screening (ECS).
• Careful selection of genes and clear guidelines for variant reporting, including VUS, are crucial.
• Ongoing evaluation and updates are essential for effective ECS implementation.