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Scott A. Rivkees, Karl Hager, Seiyu Hosono, Anastasia Wise, Peining Li, Henry M. Rinder, Jeffrey R. Gruen, A Highly Sensitive, High-Throughput Assay for the Detection of Turner Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 3, 1 March 2011, Pages 699–705, https://doi.org/10.1210/jc.2010-1554
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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.
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.
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.
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.
