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Gepubliceerd in: Journal of Autism and Developmental Disorders 5/2005

01-10-2005

Brief Report: Non-Random X Chromosome Inactivation in Females with Autism

Auteurs: Z. Talebizadeh, D. C. Bittel, O. J. Veatch, N. Kibiryeva, M. G. Butler

Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 5/2005

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Abstract

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.
Literatuur
go back to reference Allen R. C., Zoghbi H. Y., Moseley A. B., Rosenblatt H. M., Belmont J. W., (1992). Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation American Journal of Human Genetics 51: 1229–1239PubMed Allen R. C., Zoghbi H. Y., Moseley A. B., Rosenblatt H. M., Belmont J. W., (1992). Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation American Journal of Human Genetics 51: 1229–1239PubMed
go back to reference Azofeifa J., Voit T., Hubner C., Cremer M., (1995). X-chromosome methylation in manifesting and healthy carries of dystrophinopathies: Concordance of activation ratios among first degree female relatives and skewed inactivation as cause of the affected phenotypes Human Genetics 96: 167–176PubMedCrossRef Azofeifa J., Voit T., Hubner C., Cremer M., (1995). X-chromosome methylation in manifesting and healthy carries of dystrophinopathies: Concordance of activation ratios among first degree female relatives and skewed inactivation as cause of the affected phenotypes Human Genetics 96: 167–176PubMedCrossRef
go back to reference Brown C. J., Carrel L., Willard H. F., (1997). Expression of genes from the human active and inactive X chromosomes American Journal of Human Genetics 60: 1333–1343PubMedCrossRef Brown C. J., Carrel L., Willard H. F., (1997). Expression of genes from the human active and inactive X chromosomes American Journal of Human Genetics 60: 1333–1343PubMedCrossRef
go back to reference Brown C. J., Hendrich B. D., Rupertt J. L., Lafreniere R. G., Xing Y., Lawrence J., Willard H. F., (1992). The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus Cell 71: 527–542PubMedCrossRef Brown C. J., Hendrich B. D., Rupertt J. L., Lafreniere R. G., Xing Y., Lawrence J., Willard H. F., (1992). The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus Cell 71: 527–542PubMedCrossRef
go back to reference Brown C. J., Lafreniere R. G., Powers V. E., Sebastio G., Ballabio A., et al. (1991). Localization of the X inactivation center on the human X chromosome in Xq13 Nature 349: 82–84PubMedCrossRef Brown C. J., Lafreniere R. G., Powers V. E., Sebastio G., Ballabio A., et al. (1991). Localization of the X inactivation center on the human X chromosome in Xq13 Nature 349: 82–84PubMedCrossRef
go back to reference Carrel L., Cottle A. A., Goglin K. C., Willard H. F., (1999). A first-generation X-inactivation profile of the human X chromosome Proceedings of the National Academy of Sciences USA 7: 14440–14444CrossRef Carrel L., Cottle A. A., Goglin K. C., Willard H. F., (1999). A first-generation X-inactivation profile of the human X chromosome Proceedings of the National Academy of Sciences USA 7: 14440–14444CrossRef
go back to reference Devriendt K., Matthijs G., Legius E., Schollen E., Blockmans D., van Geet C., Degreef H., Cassiman J. J., Fryns J. P., (1997). Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita American Journal of Human Genetics 60: 581–587PubMed Devriendt K., Matthijs G., Legius E., Schollen E., Blockmans D., van Geet C., Degreef H., Cassiman J. J., Fryns J. P., (1997). Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita American Journal of Human Genetics 60: 581–587PubMed
go back to reference Harris A., Collins J., Vetrie D., Cole C., Bobrow M., (1992). X inactivation as a mechanism of selection against lethal alleles: Further investigation of incontinentia pigmenti and X linked lymphoproliferative disease Journal of Medical Genetics 29: 608–614PubMed Harris A., Collins J., Vetrie D., Cole C., Bobrow M., (1992). X inactivation as a mechanism of selection against lethal alleles: Further investigation of incontinentia pigmenti and X linked lymphoproliferative disease Journal of Medical Genetics 29: 608–614PubMed
go back to reference Ishikawa-Brush Y., Powell J. F., Bolton P., Miller A. P., Francis F., Willard H. F., Lehrach H., Monaco A. P., (1997). Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3′ to the SDC2 gene Human Molecular Genetics 6: 1241–1250PubMedCrossRef Ishikawa-Brush Y., Powell J. F., Bolton P., Miller A. P., Francis F., Willard H. F., Lehrach H., Monaco A. P., (1997). Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3′ to the SDC2 gene Human Molecular Genetics 6: 1241–1250PubMedCrossRef
go back to reference Jamain S., Quach H., Betancur C., Rastam M., Colineaux C., Gillberg I. C., Soderstrom H., Giros B., Leboyer M., Gillberg C., Bourgeron T., (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Paris Autism Research International Sibpair Study Nature Genetics 34: 27–29PubMedCrossRef Jamain S., Quach H., Betancur C., Rastam M., Colineaux C., Gillberg I. C., Soderstrom H., Giros B., Leboyer M., Gillberg C., Bourgeron T., (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Paris Autism Research International Sibpair Study Nature Genetics 34: 27–29PubMedCrossRef
go back to reference Karasawa M., Tsukamoto N., Yamane A., Okamoto K., Maehara T., Yokohama A., Nojima Y., Omine M., (2001). Analysis of the distribution of CAG repeats and X-chromosome inactivation status of HUMARA gene in healthy female subjects using improved fluorescence-based assay International Journal of Hematology 74: 281–286PubMedCrossRef Karasawa M., Tsukamoto N., Yamane A., Okamoto K., Maehara T., Yokohama A., Nojima Y., Omine M., (2001). Analysis of the distribution of CAG repeats and X-chromosome inactivation status of HUMARA gene in healthy female subjects using improved fluorescence-based assay International Journal of Hematology 74: 281–286PubMedCrossRef
go back to reference Lau A. W., Brown C. J., Penaherrera M., Langlois S., Kalousek D. K., Robinson W. P., (1997). Skewed X-chromosome inactivation is common in fetuses or newborns associated with confined placental mosaicism American Journal of Human Genetics 61: 1353–1361PubMedCrossRef Lau A. W., Brown C. J., Penaherrera M., Langlois S., Kalousek D. K., Robinson W. P., (1997). Skewed X-chromosome inactivation is common in fetuses or newborns associated with confined placental mosaicism American Journal of Human Genetics 61: 1353–1361PubMedCrossRef
go back to reference Lord C., Rutter M., Le Couteur A., (1994). Autism diagnostic interview—revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders Journal of Autism and Developmental Disorders 24: 659–685PubMedCrossRef Lord C., Rutter M., Le Couteur A., (1994). Autism diagnostic interview—revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders Journal of Autism and Developmental Disorders 24: 659–685PubMedCrossRef
go back to reference Lyon M. F., (1961). Gene action in the X-chromosome of the mouse (Mus musculus L.) Nature 190: 372–373PubMedCrossRef Lyon M. F., (1961). Gene action in the X-chromosome of the mouse (Mus musculus L.) Nature 190: 372–373PubMedCrossRef
go back to reference Maier E. M., Kammerer S., Muntau A. C., Wichers M., Braun A., Roscher A. A., (2002). Symptoms in carriers of adrenoleukodystrophy relate to skewed X inactivation Annals of Neurology 52: 683–688PubMedCrossRef Maier E. M., Kammerer S., Muntau A. C., Wichers M., Braun A., Roscher A. A., (2002). Symptoms in carriers of adrenoleukodystrophy relate to skewed X inactivation Annals of Neurology 52: 683–688PubMedCrossRef
go back to reference Migeon B. R., (1998). Non-random X chromosome inactivation in mammalian cells Cytogenetics and Cell Genetics 80: 142–148PubMedCrossRef Migeon B. R., (1998). Non-random X chromosome inactivation in mammalian cells Cytogenetics and Cell Genetics 80: 142–148PubMedCrossRef
go back to reference Naumova A. K., Plenge R. M., Bird L. M., Leppert M., Morgan K., Willard H. F., Sapienza C., (1996). Heritability of X chromosome—inactivation phenotype in a large family American Journal of Human Genetics 58: 1111–1119PubMed Naumova A. K., Plenge R. M., Bird L. M., Leppert M., Morgan K., Willard H. F., Sapienza C., (1996). Heritability of X chromosome—inactivation phenotype in a large family American Journal of Human Genetics 58: 1111–1119PubMed
go back to reference Penny G. D., Kay G. F., Sheardown S. A., Rastan S., Brockdorff N., (1996). Requirement for XIST in X chromosome inactivation Nature 379: 131–137PubMedCrossRef Penny G. D., Kay G. F., Sheardown S. A., Rastan S., Brockdorff N., (1996). Requirement for XIST in X chromosome inactivation Nature 379: 131–137PubMedCrossRef
go back to reference Plenge R. M., Hendrich B. D., Schwartz C., Arena F., Naumova A., Sapienza C., Winter R. M, Willard H. F., (1997). A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation Nature Genetics 17: 353–356PubMedCrossRef Plenge R. M., Hendrich B. D., Schwartz C., Arena F., Naumova A., Sapienza C., Winter R. M, Willard H. F., (1997). A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation Nature Genetics 17: 353–356PubMedCrossRef
go back to reference Plenge R. M., Stevenson R. A., Lubs H. A., Schwartz C. E., Willard H. F., (2002). Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders American Journal of Human Genetics 71: 168–173PubMedCrossRef Plenge R. M., Stevenson R. A., Lubs H. A., Schwartz C. E., Willard H. F., (2002). Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders American Journal of Human Genetics 71: 168–173PubMedCrossRef
go back to reference Rao P. N., Klinepeter K., Stewart W., Hayworth R., Grubs R., Pettenati M. J., (1994). Molecular cytogenetic analysis of duplication Xp in a male: Further delineation of a possible sex influencing region on the X chromosome Human Genetics 94: 149–153PubMedCrossRef Rao P. N., Klinepeter K., Stewart W., Hayworth R., Grubs R., Pettenati M. J., (1994). Molecular cytogenetic analysis of duplication Xp in a male: Further delineation of a possible sex influencing region on the X chromosome Human Genetics 94: 149–153PubMedCrossRef
go back to reference Russell L. B., (1963). Mammalian X-chromosome action: Inactivation limited in spread and region of origin Science 140: 976–978PubMedCrossRef Russell L. B., (1963). Mammalian X-chromosome action: Inactivation limited in spread and region of origin Science 140: 976–978PubMedCrossRef
go back to reference Sangha K. K., Stephenson M. D., Brown C. J., Robinson W. P., (1999). Extremely skewed X-chromosome inactivation is increased in women with recurrent spontaneous abortion American Journal of Human Genetics, 65: 913–917PubMedCrossRef Sangha K. K., Stephenson M. D., Brown C. J., Robinson W. P., (1999). Extremely skewed X-chromosome inactivation is increased in women with recurrent spontaneous abortion American Journal of Human Genetics, 65: 913–917PubMedCrossRef
go back to reference Sun Y. J., Baumer A., (1999). Nonrandom X inactivation and selection of fragile X full mutation in fetal fibroblasts American Journal of Medical Genetics 86: 162–164PubMedCrossRef Sun Y. J., Baumer A., (1999). Nonrandom X inactivation and selection of fragile X full mutation in fetal fibroblasts American Journal of Medical Genetics 86: 162–164PubMedCrossRef
go back to reference Thomas N. S., Sharp A. J., Browne C. E., Skuse D., Hardie C., Dennis N. R., (1999). Xp deletions associated with autism in three females Human Genetics 104: 43–48PubMedCrossRef Thomas N. S., Sharp A. J., Browne C. E., Skuse D., Hardie C., Dennis N. R., (1999). Xp deletions associated with autism in three females Human Genetics 104: 43–48PubMedCrossRef
go back to reference Villard L., Levy N., Xiang F., Kpebe A., Labelle V., Chevillard C., Zhang Z., Schwartz C. E., Tardieu M., Chelly J., Anvret M., Fontes M., (2001). Segregation of a totally skewed pattern of X chromosome inactivation in four familial cases of Rett syndrome without MECP2 mutation: Implications for the disease Journal of Medical Genetics 38: 435–442PubMedCrossRef Villard L., Levy N., Xiang F., Kpebe A., Labelle V., Chevillard C., Zhang Z., Schwartz C. E., Tardieu M., Chelly J., Anvret M., Fontes M., (2001). Segregation of a totally skewed pattern of X chromosome inactivation in four familial cases of Rett syndrome without MECP2 mutation: Implications for the disease Journal of Medical Genetics 38: 435–442PubMedCrossRef
go back to reference Volkmar F. R., Szatmari P., Sparrow S. S., (1993). Sex differences in pervasive developmental disorder Journal of Autism and Developmental Disorders 23: 579–591PubMedCrossRef Volkmar F. R., Szatmari P., Sparrow S. S., (1993). Sex differences in pervasive developmental disorder Journal of Autism and Developmental Disorders 23: 579–591PubMedCrossRef
go back to reference Willard H. F., (1995). The sex chromosome and X-chromosome inactivation. In: Scriver C. R., Beaudet A. L., Sly W. S., Valle D., (Eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, 717–737 Willard H. F., (1995). The sex chromosome and X-chromosome inactivation. In: Scriver C. R., Beaudet A. L., Sly W. S., Valle D., (Eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, 717–737
go back to reference Yonan A. L., Alarcon M., Cheng R., Magnusson P. K., Spence S. J., Palmer A. A., Grunn A., Juo S. H., Terwilliger J. D., Liu J., Cantor R. M., Geschwind D. H., Gilliam T. C.. (2003). A genomewide screen of 345 families for autism-susceptibility loci American Journal of Human Genetics 73: 886–897PubMedCrossRef Yonan A. L., Alarcon M., Cheng R., Magnusson P. K., Spence S. J., Palmer A. A., Grunn A., Juo S. H., Terwilliger J. D., Liu J., Cantor R. M., Geschwind D. H., Gilliam T. C.. (2003). A genomewide screen of 345 families for autism-susceptibility loci American Journal of Human Genetics 73: 886–897PubMedCrossRef
go back to reference Yoshioka M., Yorifuji T., Mituyoshi I., (1998). Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy Clinical Genetics 53: 102–107PubMedCrossRef Yoshioka M., Yorifuji T., Mituyoshi I., (1998). Skewed X inactivation in manifesting carriers of Duchenne muscular dystrophy Clinical Genetics 53: 102–107PubMedCrossRef
Metagegevens
Titel
Brief Report: Non-Random X Chromosome Inactivation in Females with Autism
Auteurs
Z. Talebizadeh
D. C. Bittel
O. J. Veatch
N. Kibiryeva
M. G. Butler
Publicatiedatum
01-10-2005
Uitgeverij
Springer US
Gepubliceerd in
Journal of Autism and Developmental Disorders / Uitgave 5/2005
Print ISSN: 0162-3257
Elektronisch ISSN: 1573-3432
DOI
https://doi.org/10.1007/s10803-005-0011-z

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