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.
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Acknowledgments
We acknowledge the AGRE families without whom none of this research would be possible. The AGRE Program, founded by Cure Autism Now, is supported through private donations from Cure Autism Now and by a grant from the National Institute of Mental Health (NIMH) to UCLA and collaborating investigators. Continual scientific oversight is provided by the AGRE Scientific Steering Committee, chaired by Dan Geschwind, M.D., Ph.D., Director of the Neurogenetics Program, Department of Neurology, UCLA. Partial funding support for this study was from CMH Special Gift Funds (GL 01.2650).
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Talebizadeh, Z., Bittel, D., Veatch, O. et al. Brief Report: Non-Random X Chromosome Inactivation in Females with Autism. J Autism Dev Disord 35, 675–681 (2005). https://doi.org/10.1007/s10803-005-0011-z
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DOI: https://doi.org/10.1007/s10803-005-0011-z