title: Copy number changes on the X chromosome in women with and without highly skewed X-chromosome inactivation.
abstract: OBJECTIVE
  To test the hypothesis that microdeletions or microduplications below the resolution of a standard karyotype may be a significant cause of highly skewed X-inactivation (HSXI) in women without a cytogenetically detected X-chromosome anomaly.
  
  
  METHODS
  Cases were women with HSXI, defined as ≥85% of cells in a blood sample with the same active allele at the HUMARA locus. The skewing in controls ranged from 50 to <75%. We performed an SNP microarray analysis using the Affymetrix 6.0 platform for 45 cases and 45 controls.
  
  
  RESULTS
  Cases and controls did not differ in the frequency of X-chromosome copy number changes ≥100 kb or in the frequency of copy number changes that contained genes. However, one woman with HSXI >90% in blood and left and right buccal smears had a 5.5-Mb deletion in Xp22.2p22.1. This deletion could affect the viability of male conceptions and may have led to the dysmorphology found in female carriers.
  
  
  CONCLUSIONS
  HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.
authors.affiliation: Department of Pathology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. vj2004@columbia.edu
authors.forename: V
authors.initials: V
authors.lastname: Jobanputra
authors.forename: B
authors.initials: B
authors.lastname: Levy
authors.forename: A
authors.initials: A
authors.lastname: Kinney
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Shirazi
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Kline
authors.forename: D
authors.initials: D
authors.lastname: Warburton
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics; D014314:Trisomy / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen