title: Ending the late diagnosis of Turner syndrome through a novel high-throughput assay.
abstract: 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 growth hormone; however, many girls with TS are not detected until after 10 years of age resulting in delayed evaluation and treatment. To facilitate the detection of TS, we developed a high-throughput test for TS, based on a quantitative method of genotyping to detect X-chromosome abnormalities. This test utilizes pyrosequencing to quantitate relative allele strength (RAS) from single nucleotide polymorphisms (SNPs) using 18 informative SNP markers that span the X-chromosome and one marker for the detection of Y-chromosome material. 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 72 females without TS and 69 females with TS. In this group, TS was identified with 97.1 sensitivity and 90.3% 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.
authors.affiliation: Yale Child Health Research Center, Department of Pediatrics Yale University School of Medicine. New Haven, CT 06520, USA. Scott.Rivkees@Yale.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D057210:Delayed Diagnosis / Q000517:prevention & control*; D042241:Early Diagnosis; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics