Document Detail


A highly sensitive, high-throughput assay for the detection of Turner syndrome.
MedLine Citation:
PMID:  21177792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Scott A Rivkees; Karl Hager; Seiyu Hosono; Anastasia Wise; Peining Li; Henry M Rinder; Jeffrey R Gruen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-22
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  96     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2011-05-23     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  699-705     Citation Subset:  AIM; IM    
Affiliation:
Yale Child Health Research Center, Yale University School of Medicine, 464 Congress Avenue, New Haven, Connecticut 06520, USA. Scott.Rivkees@Yale.edu
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MeSH Terms
Descriptor/Qualifier:
Alleles
Chromosomes, Human, X / genetics
Chromosomes, Human, Y / genetics
Cohort Studies
DNA / genetics
Female
Genotype
High-Throughput Screening Assays
Homozygote
Humans
Karyotyping
Male
Mouth Mucosa / chemistry
Polymorphism, Single Nucleotide
Reproducibility of Results
Turner Syndrome / diagnosis*,  genetics*
Grant Support
ID/Acronym/Agency:
R42HD049230/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
9007-49-2/DNA
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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