An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening.

Area of Science:

• Genomics
• Medical Genetics
• Public Health

Background:

• Newborn screening aims to identify genetic disorders early for timely intervention.
• Genomic sequencing offers potential for broader newborn screening but requires robust evaluation methods.
• Assessing clinical actionability of gene-disease pairs is crucial for effective newborn screening.

Purpose of the Study:

• To evaluate a novel, age-based metric for scoring clinical actionability of gene-disease pairs.
• To compare this metric's performance against established newborn screening evaluation methods.
• To inform decisions regarding the inclusion of genomic sequencing in newborn screening programs.

Main Methods:

• Development of an age-based, semiquantitative metric to assess clinical actionability.
• Classification of 822 gene-disease pairs based on age of onset and actionability.
• Comparison of the novel metric with the Recommended Uniform Screening Panel (RUSP) and other contemporary methods.

Main Results:

• 466 gene-disease pairs were classified as having childhood onset and high actionability, similar to RUSP core panel conditions.
• 245 pairs had childhood onset and low/no actionability; 25 had adult onset and high actionability.
• 67 pairs were excluded due to controversial evidence or prenatal onset.

Conclusions:

• The developed age-based metric provides a standardized approach for evaluating gene-disease pairs for newborn screening.
• This metric can assist in making informed decisions about incorporating genomic sequencing into newborn screening.
• The findings support the use of genomic data for personalized genetic screening in newborns.