A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation

Nat Genet. 1997 Nov;17(3):353-6. doi: 10.1038/ng1197-353.


X-chromosome inactivation is the process by which a cell recognizes the presence of two copies of an X chromosome early in the development of XX embryos and chooses one to be active and one to be inactive. Although it is commonly believed that the initiation of X inactivation is random, with an equal probability (50:50) that either X chromosome will be the inactive X in a given cell, significant variation in the proportion of cells with either X inactive is observed both in mice heterozygous for alleles at the Xce locus and among normal human females in the population. Families in which multiple females demonstrate extremely skewed inactivation patterns that are otherwise quite rare in the general population are thought to reflect possible genetic influences on the X-inactivation process. Here we report a rare cytosine to guanine mutation in the XIST minimal promoter that underlies both epigenetic and functional differences between the two X chromosomes in nine females from two unrelated families. All females demonstrate preferential inactivation of the X chromosome carrying the mutation, suggesting that there is an association between alterations in the regulation of XIST expression and X-chromosome inactivation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Deoxyribonucleases, Type II Site-Specific / genetics
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Dosage Compensation, Genetic*
  • Female
  • Haplotypes
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Promoter Regions, Genetic
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Receptors, Androgen / genetics
  • Transcription Factors / genetics*


  • RNA, Long Noncoding
  • RNA, Untranslated
  • Receptors, Androgen
  • Transcription Factors
  • XIST non-coding RNA
  • Deoxyribonucleases, Type II Site-Specific
  • GCGC-specific type II deoxyribonucleases