A highly sensitive, high-throughput assay for the detection of Turner syndrome
Open accessAbstract
OBJECTIVE: Turner syndrome (TS) occurs when an X-chromosome is completely or partially deleted or when X-chromosomal mosaicism is present. Girls with TS benefit from early diagnosis and treatment with GH; however, many girls with TS are not detected until after 10 yr of age, resulting in delayed evaluation and treatment. METHODS: We developed a high-throughput test for TS, based on a quantitative method of genotyping to detect X-chromosome abnormalities. This test uses pyrosequencing to quantitate relative allele strength (RAS) from single-nucleotide polymorphisms using 18 informative single-nucleotide polymorphisms markers that span the X-chromosome and one marker for the detection of Y-chromosome material. RESULTS: Cutoff ranges for heterozygous, homozygous, or out-of-range RAS values were established from a cohort of 496 males and females. Positive TS scoring criteria were defined as the presence of homozygosity for all 18 markers or the presence of at least one out-of-range RAS value. To determine the validity of this rapid test for TS detection, we undertook a large-scale study using DNA from 132 females without TS and 74 females with TS for whom karyotypes were available. TS was identified with 96.0% sensitivity and 97.0% specificity in this cohort. We also tested buccal swab DNA from a group of 19 females without TS and 69 females with TS. In this group, TS was identified with 97.1% sensitivity and 84.2% specificity. CONCLUSIONS: These results demonstrate the validity of a high-throughput, pyrosequencing based test for the accurate detection of TS, providing a potential alternative to karyotype testing.
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Several molecular methods have been proposed for neonatal screening of TS, the most promising of which thus far are pyrosequencing and real-time PCR.
“Alternatively, several molecular methods have been proposed for neonatal screening of TS, the most promising of which thus far are pyrosequencing and real-time PCR.89”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [89]
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- Authors
- Rivkees, S. A., Hager, K., Hosono, S., Wise, A., Li, P., Rinder, H. M., & Gruen, J. R.
- Affiliations
- Yale University (US)
- JS Genetics (United States) (US)
- Corresponding author
- Rivkees, Scott A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-03-01
- Volume
- 96
- Issue
- 3
- Pages
- 699-705
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3047225
- OpenAlex
- W2045253224
- Cited by
- 28
- References
- 27
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R42HD049230)
- 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 › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Turner syndrome, X chromosome deletion, pyrosequencing, SNP markers, buccal swab DNA, early diagnosis, growth hormone therapy, sensitivity and specificity
- MeSH terms
- Alleles, DNA, Female, Genotype, Homozygote, Humans, Karyotyping, Male, Mouth Mucosa, Turner Syndrome, Reproducibility of Results, Cohort Studies, Polymorphism, Single Nucleotide, Chromosomes, Human, X, Chromosomes, Human, Y, High-Throughput Screening Assays
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