WES-based screening of 7,000 newborns: A pilot study in Russia

Area of Science:

• Genetics
• Genomics
• Pediatrics

Background:

• Next-generation sequencing (NGS) costs are decreasing, enabling its use in newborn screening.
• Conventional newborn screening detects limited diseases, while NGS can screen thousands of genes.
• Ethical and interpretation challenges exist for screening healthy infants using NGS.

Purpose of the Study:

• To assess the feasibility and findings of large-scale NGS-based genetic screening in healthy newborns.
• To identify clinically significant variants in infants, including those with early-onset, adult-onset, and chromosomal conditions.
• To address variant interpretation issues in presumed healthy newborns.

Main Methods:

• Whole-exome and whole-genome sequencing were used for genetic screening.
• The study included 7,000 apparently healthy infants screened for variants in 2,350 genes.
• Variants associated with early-onset, adult-onset, and chromosomal abnormalities were analyzed.

Main Results:

• Clinically significant variants for early-onset treatable diseases were found in 0.9% of infants.
• Variants linked to adult-onset diseases were identified in 2.1% of newborns.
• Chromosomal abnormalities were detected in 0.3% of the screened infants.

Conclusions:

• Large-scale NGS newborn screening identifies a significant proportion of infants with actionable genetic findings.
• The study demonstrates the potential of NGS for expanding newborn screening beyond conventional methods.
• Further research is needed to address variant interpretation and clinical management strategies for identified variants in healthy infants.