Gene selection for genomic newborn screening: Moving toward consensus?

Area of Science:

• Genetics
• Genomics
• Medical Genetics

Background:

• Gene selection is crucial for the validity and ethical use of genomic newborn screening (gNBS).
• Existing gNBS gene lists show significant variability despite shared selection principles.
• Harmonizing gene lists is essential for consistent and reliable gNBS implementation.

Purpose of the Study:

• To curate a consensus gene list for genomic newborn screening (gNBS).
• To build upon existing efforts and establish a core list of gene-disease pairs.
• To facilitate international harmonization of gNBS gene selection.

Main Methods:

• A multidisciplinary expert team curated a gene list using an open platform and existing resources.
• Inclusion criteria focused on severe, treatable disorders with early onset (<5 years) and established gene-disease associations.
• The curated list was compared with five other gNBS projects to identify consensus and discrepancies.

Main Results:

• 1279 genes were reviewed, with 604 meeting inclusion criteria.
• Metabolic conditions (25%), immunodeficiencies (21%), and endocrine disorders (15%) were the largest groups.
• 55 consensus genes were identified across all six gNBS projects, with discrepancies often due to variable definitions of treatability and gene-disease association strength.

Conclusions:

• A consensus gene list for gNBS has been identified.
• This list provides a foundation for international harmonization efforts in gNBS.
• Standardizing gene selection will enhance the reliability and ethical application of gNBS.