AI Article Synopsis
- Newborn screening for spinal muscular atrophy (SMA) traditionally relies on PCR assays to detect a specific genetic deletion, but challenges in DNA mapping have limited the use of next-generation sequencing (NGS).
- Recent advancements in bioinformatics and NGS technology allow for accurate analysis of dried blood spot samples, but larger scale implementations for population screening have been lacking.
- A study involving over 2,500 newborns demonstrated that integrating NGS with custom algorithms facilitated effective SMA screening, suggesting that this approach could be expanded to simultaneously test for multiple genetic conditions.
Article Abstract
Newborn screening (NBS) assays for spinal muscular atrophy (SMA) typically use a polymerase chain reaction (PCR) based assay to identify individuals with homozygous deletion in exon 7 of the gene. Due to high DNA sequence homology between and , it has previously been difficult to accurately bioinformatically map short reads from next-generation DNA sequencing (NGS) to , resulting in low analytical performance and preventing NGS being used for SMA screening. Advances in bioinformatics have allowed NGS to be used in diagnostic settings, but to date these assays have not reached the scale required for high volume population newborn screening and have not been performed on the dried blood spot samples that NBS programs currently use. Here we integrate an NGS assay using hybridisation-based capture with a customised bioinformatics algorithm and purpose designed high throughput reporting software into an existing NBS program to achieve a laboratory workflow for population SMA screening. We tested the NGS assay on over 2500 newborns born over 2 weeks in a NBS program in a technical feasibility study and show high sensitivity and specificity. Our results suggest NGS may be an alternate method for SMA screening by NBS programs, providing a multiplex testing platform on which potentially hundreds of inherited conditions could be simultaneously tested.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878289 | PMC |
| http://dx.doi.org/10.3389/fgene.2023.1095600 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Retrospective observational cohort study of premature neonates screened for ROP with 7 years of follow-up assessing the visual outcomes and adequacy of preschool visual screening.
BMJ Open Ophthalmol
December 2024
Ophthalmology, Royal Hospital for Children, Glasgow, UK.
Background: Very premature infants screened for retinopathy of prematurity (ROP) that do not develop ROP still experience serious visual developmental challenges, and while it is recommended that all children in the UK are offered preschool visual screening, we aimed to explore whether this vulnerable group requires dedicated follow-up.
Methods: We performed a real-world retrospective observational cohort study of children previously screened for ROP in NHS Greater Glasgow and Clyde (Scotland) between 2013 and 2015. We excluded those with any severity of ROP identified during screening.
Distribution of Pathogens in Early- and Late-Onset Sepsis Among Preterm Infants: A Decade-Long Study in a Tertiary Referral Neonatal Intensive Care Unit.
J Clin Med
December 2024
Department of Neonatology, Faculty of Medicine, Ludwik Rydgier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Ujejskiego 75, 85-168 Bydgoszcz, Poland.
Neonatal sepsis, a severe infection in newborns, remains one of the leading causes of morbidity and mortality among preterm infants. This study aimed to investigate the distribution of pathogens responsible for early-onset sepsis (EOS) and late-onset sepsis (LOS), the annual variability of pathogens responsible for each type of infection, and potential trends in their profiles in preterm infants from a tertiary care neonatal intensive care unit over a ten-year period. We analyzed 177 episodes of confirmed bloodstream infection between 1 January 2014 and 31 December 2023.
View Article and Find Full Text PDFNovel Variants Related to a Variable Phenotypic Spectrum Ranging from Epilepsy with Auditory Features to Severe Developmental and Epileptic Encephalopathies.
Int J Mol Sci
December 2024
Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, 88100 Catanzaro, Italy.
Pathogenic variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to -developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.
View Article and Find Full Text PDFPushing the boundaries: future directions in the management of spinal muscular atrophy.
Trends Mol Med
January 2025
MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, OX3 9DU, UK; NIHR Oxford Biomedical Research Centre, Oxford, OX3 9DU, UK; Neuromuscular Centre, Division of Paediatrics, University Hospital of Liège and University of Liège, 4000, Liège, Belgium. Electronic address:
Spinal muscular atrophy (SMA) is a devastating, degenerative, paediatric neuromuscular disease which until recently was untreatable. Discovery of the responsible gene 30 years ago heralded a new age of pioneering therapeutic developments. Three disease-modifying therapies (DMTs) have received regulatory approval and have transformed the disease, reducing disability and prolonging patient survival.
View Article and Find Full Text PDFEvaluating the Utility of Initial Exams in Retinopathy of Prematurity: Proposal of FIRST-ROP Algorithm for a Medium-Risk Cohort.
Ophthalmology
January 2025
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA. Electronic address:
Purpose: To assess the utility of the first or second examinations for retinopathy of prematurity (ROP) in a medium-risk cohort of infants and to propose an optimization to the current ROP screening guidelines.
Design: Retrospective consecutive study.
Subjects: Infants screened for ROP between January 2017 and August 2023 at three different tertiary-level care neonatal intensive care units.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!