title: A highly sensitive, high-throughput assay for the detection of Turner syndrome.
abstract: 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.
authors.affiliation: Yale Child Health Research Center, Yale University School of Medicine, 464 Congress Avenue, New Haven, Connecticut 06520, USA. Scott.Rivkees@Yale.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
authors.forename: Karl
authors.initials: K
authors.lastname: Hager
authors.forename: Seiyu
authors.initials: S
authors.lastname: Hosono
authors.forename: Anastasia
authors.initials: A
authors.lastname: Wise
authors.forename: Peining
authors.initials: P
authors.lastname: Li
authors.forename: Henry M
authors.initials: HM
authors.lastname: Rinder
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
mesh_terms: D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D057166:High-Throughput Screening Assays; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D008297:Male; D009061:Mouth Mucosa / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D004247:DNA