title: Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.
abstract: BACKGROUND
  Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection.
  
  
  METHODS
  The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs.
  
  
  RESULTS
  Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS.
  
  
  CONCLUSIONS
  XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids.
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China; Shanghai Center for Women and Children's Health, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Children Hospital of Fudan University, Shanghai, China; Shanghai Key Laboratory of Prevention and Intervention of Birth Defects, Shanghai, China. Electronic address: xzzhao@fudan.edu.cn.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010865:Pilot Projects; D017422:Sequence Analysis, DNA; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
keywords: DNA methylation; Turner syndrome; X chromosome aneuploids; X-chromosome inactivation