Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

SummaryWhole-genome and whole-exome sequencing for clinical applications is now an integral part of medical genetics practice. The term newborn screening refers to public health programs designed to screen newborns for various treatable metabolic conditions, by measuring levels of circulating blood metabolites. The availability and significant decrease in sequencing costs has raised the question of whether metabolic newborn screening should be replaced by whole-genome or whole-exome sequencing. While newborn genome sequencing can potentially increase the number of disorders identified by newborn screening, the generalization of its practice raises a number of important ethical issues. This short article argues that there are medical, psychological, ethical and economic reasons why widespread dissemination of newborn screening is still premature.

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An Easily Overlooked Contamination of Syringes in Newborn Screening by Tandem Mass Spectrometry

Frontiers in Pediatrics ◽

10.3389/fped.2020.596321 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yanyun Wang ◽

Yun Sun ◽

Tao Jiang

Keyword(s):

Mass Spectrometry ◽

Quality Control ◽

Tandem Mass Spectrometry ◽

Newborn Screening ◽

Retrospective Analysis ◽

Tandem Mass ◽

Patient Sample ◽

Important Test ◽

Control Samples

Background: Tandem mass spectrometry becomes a common and important test in newborn screening, but potential contamination of the equipment has largely been ignored.Methods: The source of contamination through Biosan quality control samples was examined prospectively, and further confirmed by retrospective analysis of patient samples.Results: We found that the source of contamination came from a syringe in the Biosan quality control samples. Furthermore, we found that a large number of indicators in the patient sample were interfered by syringe contamination in our center, and also in two other newborn screening centers, but the affected indicators were different in different screening centers.Conclusion: Syringe contamination will affect the detection of patient samples by tandem mass spectrometry and should be monitored carefully and immediately.

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The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health

Frontiers in Pediatrics ◽

10.3389/fped.2021.663752 ◽

2021 ◽

Vol 9 ◽

Author(s):

Audrey C. Woerner ◽

Renata C. Gallagher ◽

Jerry Vockley ◽

Aashish N. Adhikari

Keyword(s):

Newborn Screening ◽

Exome Sequencing ◽

Genetic Disorders ◽

Population Based ◽

Lessons Learned ◽

Screening Tests ◽

Whole Genome ◽

Whole Exome ◽

Challenges And Opportunities ◽

History Of

Newborn screening (NBS) is a population-based program with a goal of reducing the burden of disease for conditions with significant clinical impact on neonates. Screening tests were originally developed and implemented one at a time, but newer methods have allowed the use of multiplex technologies to expand additions more rapidly to standard panels. Recent improvements in next-generation sequencing are also evolving rapidly from first focusing on individual genes, then panels, and finally all genes as encompassed by whole exome and genome sequencing. The intersection of these two technologies brings the revolutionary possibility of identifying all genetic disorders in newborns, allowing implementation of therapies at the optimum time regardless of symptoms. This article reviews the history of newborn screening and early studies examining the use of whole genome and exome sequencing as a screening tool. Lessons learned from these studies are discussed, along with technical, ethical, and societal challenges to broad implementation.

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Enzyme Diagnostics in a Changing World of Exome Sequencing and Newborn Screening as Exemplified for Peroxisomal, Mitochondrial, and Lysosomal Disorders

Inherited Metabolic Diseases ◽

10.1007/978-3-662-49410-3_38 ◽

2016 ◽

pp. 461-487

Author(s):

Ronald J. A. Wanders ◽

Ben J. H. M. Poorthuis ◽

Richard J. T. Rodenburg

Keyword(s):

Newborn Screening ◽

Exome Sequencing ◽

Lysosomal Disorders ◽

Changing World

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Abstract LB-353: Mutational profile of metastatic breast cancers using whole-exome sequencing: a retrospective analysis of 216 samples from SAFIR01 / 02 / SHIVA / MOSCATO trials

10.1158/1538-7445.am2016-lb-353 ◽

2016 ◽

Author(s):

Maud Kamal ◽

Celine Lefebvre ◽

Thomas Bachelot ◽

Thomas Filleron ◽

Marion Pedrero ◽

...

Keyword(s):

Exome Sequencing ◽

Retrospective Analysis ◽

Whole Exome Sequencing ◽

Metastatic Breast ◽

Breast Cancers ◽

Whole Exome

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Whole-Exome Sequencing for Diagnosis of Turner Syndrome: Toward Next-Generation Sequencing and Newborn Screening

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-3414 ◽

2017 ◽

Vol 102 (5) ◽

pp. 1529-1537 ◽

Cited By ~ 13

Author(s):

David R. Murdock ◽

Frank X. Donovan ◽

Settara C. Chandrasekharappa ◽

Nicole Banks ◽

Carolyn Bondy ◽

...

Keyword(s):

Next Generation Sequencing ◽

Newborn Screening ◽

Exome Sequencing ◽

Turner Syndrome ◽

Whole Exome Sequencing ◽

Genomic Research ◽

Next Generation ◽

Low Level ◽

Whole Exome ◽

Generation Sequencing

Abstract Context: Turner syndrome (TS) is due to a complete or partial loss of an X chromosome in female patients and is not currently part of newborn screening (NBS). Diagnosis is often delayed, resulting in missed crucial diagnostic and therapeutic opportunities. Objectives: This study sought to determine if whole-exome sequencing (WES) as part of a potential NBS program could be used to diagnose TS. Design, Setting, Patients: Karyotype, chromosomal microarray, and WES were performed on blood samples from women with TS (n = 27) enrolled in the Personalized Genomic Research study at the National Institutes of Health. Female control subjects (n = 37) and male subjects (n = 27) also underwent WES. Copy number variation was evaluated using EXCAVATOR2 and B allele frequency was calculated from informative single nucleotide polymorphisms. Simulated WES data were generated for detection of low-level mosaicism and complex structural chromosome abnormalities. Results: We detected monosomy for chromosome X in all 27 TS samples, including 1 mosaic for 45,X/46,XX and another with previously unreported material on chromosome Y. Sensitivity and specificity were both 100% for the diagnosis of TS with no false-positive or false-negative results. Using simulated WES data, we detected isochromosome Xq and low-level mosaicism as low as 5%. Conclusion: We present an accurate method of diagnosing TS using WES, including cases with low-level mosaicism, isochromosome Xq, and cryptic Y-chromosome material. Given the potential use of next-generation sequencing for NBS in many different diseases and syndromes, we propose WES can be used as a screening test for TS in newborns.

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