Next-generation sequencing based newborn screening and comparative analysis with MS/MS.

Area of Science:

• Genetics
• Genomics
• Medical Diagnostics

Background:

• Newborn screening (NBS) methods like tandem mass spectrometry (MS/MS) can produce false results.
• Next-generation sequencing (NGS) presents an opportunity for enhanced data output and broader applications in NBS.

Purpose of the Study:

• To analyze pathogenic gene mutation types and distribution in newborns in Huzhou, China.
• To evaluate the applicability of NGS and MS/MS in newborn screening.

Main Methods:

• Collected blood spot samples from 1263 newborns.
• Employed NGS for screening 542 disease-causing genes, validated by Sanger sequencing.
• Screened 26 inherited metabolic diseases (IMD) using MS/MS and cross-referenced positive/suspicious results with NGS.

Main Results:

• NGS detected gene mutations in 74.0% (935/1263) of newborns; pathogenic/likely pathogenic mutations were found in 20.6% (260/1263).
• MS/MS identified 18 IMD cases, but NGS verification showed no pathogenic mutations, indicating a 1.4% false positive rate for MS/MS.
• FLG, GJB2, UGT1A1, USH2A, and DUOX2 were the most frequently mutated genes detected by NGS.

Conclusions:

• NGS expands the scope of NBS and improves diagnostic accuracy over MS/MS for IMD.
• Integrating NGS with biochemical screening methods can significantly enhance the efficiency of current NBS programs.