Skewed X-chromosome inactivation is common in fetuses or newborns associated with confined placental mosaicism

Am J Hum Genet. 1997 Dec;61(6):1353-61. doi: 10.1086/301651.


The inactivation of one X chromosome in females is normally random with regard to which X is inactivated. However, exclusive or almost-exclusive inactivation of one X may be observed in association with some X-autosomal rearrangements, mutations of the XIST gene, certain X-linked diseases, and MZ twinning. In the present study, a methylation difference near a polymorphism in the X-linked androgen-receptor gene was used to investigate the possibility that nonrandom X inactivation is increases in fetuses and newborns that are associated with confined placental mosaicism (CPM) involving an autosomal trisomy. Extreme skewing was observed in 7 (58%) of 12 cases with a meiotic origin of the trisomy, but in none of 10 cases examined with a somatic origin of the trisomy, and in only 1 (4%) of 27 control adult females. In addition, an extremely skewed X-inactivation pattern was observed in 3 of 10 informative cases of female uniparental disomy (UPD) of chromosome 15. This may reflect the fact that a proportion of UPD cases arise by "rescue" of a chromosomally abnormal conceptus and are therefore associated with CPM. A skewed pattern of X inactivation in CPM cases is hypothesized to result from a reduction in the size of the early-embryonic cell pool, because of either poor early growth or subsequent selection against the trisomic cells. Since approximately 2% of pregnancies detected by chorionic villus sampling are associated with CPM, this is likely a significant contributor to both skewed X inactivation observed in the newborn population and the expression of recessive X-linked diseases in females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chorionic Villi Sampling
  • DNA Methylation
  • Dosage Compensation, Genetic*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Fetus / metabolism*
  • Gene Expression Regulation, Developmental*
  • Humans
  • Infant, Newborn
  • Maternal Age
  • Meiosis
  • Mosaicism*
  • Organ Specificity
  • Placenta / ultrastructure*
  • Pregnancy
  • Receptors, Androgen / genetics
  • Trisomy*


  • Receptors, Androgen