Brief report: non-random X chromosome inactivation in females with autism

J Autism Dev Disord. 2005 Oct;35(5):675-81. doi: 10.1007/s10803-005-0011-z.


Autism is a heterogeneous neurodevelopmental disorder with a 3-4 times higher sex ratio in males than females. X chromosome genes may contribute to this higher sex ratio through unusual skewing of X chromosome inactivation. We studied X chromosome skewness in 30 females with classical autism and 35 similarly aged unaffected female siblings as controls using the polymorphic androgen receptor (AR) gene. Significantly, increased X chromosome skewness (e.g., >80:20%) was detected in our autism group (33%) compared to unaffected females (11%). X chromosome skewness was also seen in 50% of the mothers with autistic daughters. No mutation was seen in the promoter region of the XIST gene reported to be involved in X chromosome inactivation in our subjects. X chromosome skewness has been reported in female carriers of other neurological disorders such as X-linked mental retardation, adrenoleukodystrophy and Rett syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Point Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • X Chromosome Inactivation / genetics*


  • RNA, Long Noncoding
  • RNA, Untranslated
  • XIST non-coding RNA