Copy number changes on the X chromosome in women with and without highly skewed X-chromosome inactivation

Cytogenet Genome Res. 2012;136(4):264-9. doi: 10.1159/000337920. Epub 2012 Apr 20.


Aim: 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.

Conclusion: HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abortion, Spontaneous / genetics
  • Adult
  • Case-Control Studies
  • Chromosomes, Human, X / genetics*
  • Female
  • Gene Dosage*
  • Humans
  • Infant, Newborn
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Receptors, Androgen / genetics
  • Trisomy / genetics
  • X Chromosome Inactivation*


  • AR protein, human
  • Receptors, Androgen