Brief report: non-random X chromosome inactivation in females with autism.
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.
Talebizadeh
Z
Z
Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, MO 64108, USA.
Bittel
D C
DC
Veatch
O J
OJ
Kibiryeva
N
N
Butler
M G
MG
D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA