Whole-Exome Sequencing for Diagnosis of Turner Syndrome: Toward Next-Generation Sequencing and Newborn Screening
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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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Whole-exome sequencing has been shown to accurately diagnose TS, including cases with low-level mosaicism, isochromosome Xq, and cryptic Y material.
“Whole-exome sequencing has also been shown to accurately diagnose TS, including cases with low-level mosaicism, isochromosome Xq, and cryptic Y material.94”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [94]
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Self-citation
- Authors
- Murdock, D. R., Donovan, F. X., Chandrasekharappa, S. C., Banks, N., Bondy, C., Muenke, M., & Kruszka, P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kruszka, Paul
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-01-24
- Volume
- 102
- Issue
- 5
- Pages
- 1529-1537
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5443329
- OpenAlex
- W2611282821
- Cited by
- 34
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 1
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Keywords
- Turner syndrome, exome sequencing, newborn screening, X chromosome monosomy, 45,X/46,XX mosaicism, isochromosome Xq, copy number variation, B-allele frequency, sensitivity and specificity, simulated sequencing data
- MeSH terms
- Adult, Aged, Female, Humans, Infant, Newborn, Karyotyping, Male, Middle Aged, Mosaicism, Sensitivity and Specificity, Turner Syndrome, Neonatal Screening, Case-Control Studies, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Chromosomes, Human, X, Microarray Analysis, Young Adult, High-Throughput Nucleotide Sequencing, Exome
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