Newborn screening for genetic disorders: Current status and prospects for the future

Abstract

Newborn screening (NBS) is a public health service aimed at identifying infants with severe genetic disorders, thus providing effective treatment early enough to prevent or ameliorate the onset of symptoms. Current NBS uses biochemical analysis of dried blood spots, predominately with timeresolved fluorescence immunoassay and tandem mass spectrometry, which produces some false positives and false negatives. The application of enzymatic activity-based testing technology provides a reliable screening method for some disorders. Genetic testing is now commonly used for secondary or confirmatory testing after a positive result in some NBS programs. Recently, next-generation sequencing (NGS) has emerged as a robust tool that enables large panels of genes to be scanned together rapidly. Rapid advances in NGS emphasize the potential for genomic sequencing to improve NBS programs. However, some challenges still remain and require solution before this is applied for population screening.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Chinese researchers continue to report results of pilot studies of various gene panels potentially applicable to genetic NBS: a 573-gene panel in combination with biochemical screening [ 471 ]; a 134-gene panel for 74 inborn disorders [ 472 ]; a 465-gene panel for 596 disorders as part of the Newborn Screening with Targeted Sequencing (NESTS) program in eight hospitals across China and one hospital in Beijing [ 473 ]; and a 135-gene panel for 75 disorders [ 474 ]. Related reports provide updates on the current status of genetic NBS and a look at the future [ 475 ], the use of NGS as a first-tier screening test [ 476 ]; the current attitudes and preconceptions on genetic NBS in the Chinese reproductive-aged population [ 477 ], the value of combining traditional NBS and genetic screening to reduce false negatives and to improve the early/accurate identification of CH [ 478 ], the viability of incorporating genetic screening for neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) into the current NBS program [ 479 ]; and the identification of increased numbers of actionable variants with fewer false-positive NBS results with WGS [ 480 ].…”

Newborn Screening in Developing Countries: The Need of the Hour

“…The usage of genetic testing in NBS has increased recently due to the tremendous advancements in this field. In general, diseases with unusual clinical presentations, complex phenotypes, and multigene pathogenicity can be treated with technologies like Sanger sequencing, quantitative polymerase chain reaction (qPCR), and NGS sequencing, which includes panel sequencing, whole-exome sequencing, and whole-genome sequencing [ 19 ]. When compared to genetic testing, NGS is a highly efficient method as it simultaneously sequences huge panels of genes in a single assay.…”

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

“…Recommendations for the treatment of the same cancer species of different molecular types are also different. [8][9][10] The mismatch repair (MMR)/microsatellite instability (MSI) system is the most important indicator for CRC classification, which is used to formulate treatment strategies. MSI is a code-shifting mutation of microsatellites in tumor cells caused by the insertion or deletion of duplicate units.…”