Analytical Validation of a Genomic Newborn Screening Workflow.

Area of Science:

• Genomics
• Medical Diagnostics
• Rare Diseases

Background:

• Newborn screening (NBS) currently misses many treatable rare diseases due to technical limitations.
• Conventional biochemical screening methods have inherent limitations in detecting a wide spectrum of rare conditions.

Purpose of the Study:

• To analytically validate a gene panel sequencing workflow for expanding NBS.
• To assess the feasibility, accuracy, and scalability of gene panel sequencing for detecting treatable rare diseases.

Main Methods:

• Analytical validation using dried blood spots from newborns.
• Implementation of strict quality control for sequencing, coverage, and contamination.
• Longitudinal monitoring of performance across over 5900 samples.

Main Results:

• The gene panel sequencing workflow demonstrated high sensitivity, precision, and reproducibility.
• Automated DNA extraction enhanced scalability, and panel redesign improved target region coverage.
• Focusing on known pathogenic variants minimized false positives, maintaining clinical actionability.

Conclusions:

• Gene panel sequencing-based NBS is a feasible and accurate method for expanding screening.
• This approach effectively addresses critical gaps in current newborn screening programs for rare diseases.
• The validated workflow offers a scalable solution for broader NBS coverage.