Research Article

Analysis of X chromosome inactivation in autism spectrum disorders†‡

  1. Xiaohong Gong1,
  2. Elena Bacchelli2,3,
  3. Francesca Blasi2,
  4. Claudio Toma2,
  5. Catalina Betancur4,5,
  6. Pauline Chaste1,
  7. Richard Delorme1,
  8. Christelle M. Durand1,
  9. Fabien Fauchereau1,6,
  10. Hany Goubran Botros1,
  11. Marion Leboyer4,5,7,
  12. Marie-Christine Mouren-Simeoni8,
  13. Gudrun Nygren9,
  14. Henrik Anckarsäter9,
  15. Maria Rastam9,
  16. I. Carina Gillberg9,
  17. Christopher Gillberg9,10,
  18. Daniel Moreno-De-Luca2,§,
  19. Simona Carone3,
  20. Ilona Nummela11,
  21. Mari Rossi11,
  22. Agatino Battaglia12,
  23. The International Molecular Genetic Study of Autism Consortium (IMGSAC),
  24. Irma Jarvela10,13,
  25. Elena Maestrini2,3,
  26. Thomas Bourgeron1,6,*

Article first published online: 24 MAR 2008

DOI: 10.1002/ajmg.b.30688

Issue

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Volume 147B, Issue 6, pages 830–835, 5 September 2008

Additional Information

How to Cite

Gong, X., Bacchelli, E., Blasi, F., Toma, C., Betancur, C., Chaste, P., Delorme, R., Durand, C. M., Fauchereau, F., Botros, H. G., Leboyer, M., Mouren-Simeoni, M.-C., Nygren, G., Anckarsäter, H., Rastam, M., Gillberg, I. C., Gillberg, C., Moreno-De-Luca, D., Carone, S., Nummela, I., Rossi, M., Battaglia, A., The International Molecular Genetic Study of Autism Consortium (IMGSAC), Jarvela, I., Maestrini, E. and Bourgeron, T. (2008), Analysis of X chromosome inactivation in autism spectrum disorders. Am. J. Med. Genet., 147B: 830–835. doi: 10.1002/ajmg.b.30688

Author Information

  1. 1

    Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France

  2. 2

    Department of Biology, University of Bologna, Bologna, Italy

  3. 3

    Medical Genetics Laboratory, Policlinico S.Orsola-Malpighi, Bologna, Italy

  4. 4

    INSERM, Créteil, France

  5. 5

    Université Paris, Faculté de Médecine, Créteil, France

  6. 6

    University Denis Diderot Paris 7, Paris, France

  7. 7

    Département de Psychiatrie, Groupe Hospitalier Henri Mondor et Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France

  8. 8

    Service de Psychopathologie de l'Enfant et de l'Adolescent AP-HP, Hôpital Robert Debré, Université Denis Diderot—Paris VII, Paris, France

  9. 9

    Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg, Sweden

  10. 10

    Saint George's Hospital Medical School, London, United Kingdom

  11. 11

    Department of Medical Genetics, University of Helsinki, Helsinki, Finland

  12. 12

    Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, Calambrone, Pisa, Italy

  13. 13

    Laboratory of Molecular Genetics, Helsinki University Hospital, Helsinki, Finland

  1. §

    Dr. Moreno-De-Luca was supported by a Coimbra Group Scholarship.

  2. http://www.well.ox.ac.uk/∼maestrin/iat.html.

*Human Genetics and Cognitive Functions, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France.

  1. †

    Please cite this article as follows: Gong X, Bacchelli E, Blasi F, Toma C, Betancur C, Chaste P, Delorme R, Durand CM, Fauchereau F, Botros HG, Leboyer M, Mouren-Simeoni M-C, Nygren G, Anckarsäter H, Rastam M, Gillberg IC, Gillberg C, Moreno-De-Luca D, Carone S, Nummela I, Rossi M, Battaglia A, The International Molecular Genetic Study of Autism Consortium (IMGSAC), Jarvela I, Maestrini E, Bourgeron T. 2008. Analysis of X Chromosome Inactivation in Autism Spectrum Disorders. Am J Med Genet Part B 147B:830–835.

  2. ‡

    Xiaohong Gong and Elena Bacchelli contributed equally to this work

Publication History

  1. Issue published online: 22 AUG 2008
  2. Article first published online: 24 MAR 2008
  3. Manuscript Accepted: 5 NOV 2007
  4. Manuscript Received: 31 JUL 2007

Funded by

  • Pasteur Institute
  • INSERM
  • Assistance Publique-Hôpitaux de Paris
  • FP6 AUTISM MOLGEN
  • FP6 ENI-NET
  • Fondation France Télécom
  • Fondation de France
  • Fondation biomédicale de la Mairie de Paris
  • Fondation pour la Recherche Médicale
  • The Swedish Science Council
  • Telethon-Italy. Grant Number: GP030227
  • The Academy of Finland
  • Helsinki University Hospital Research Funding

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Keywords:

  • autistic disorder;
  • skewed X-inactivation;
  • X-linked mutation;
  • linkage study

Abstract

Autism spectrum disorders (ASD) are complex genetic disorders more frequently observed in males. Skewed X chromosome inactivation (XCI) is observed in heterozygous females carrying gene mutations involved in several X-linked syndromes. In this study, we aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 163 affected girls. The XCI pattern was also determined in two control groups (144 adult females and 40 young females) with a similar age distribution to the mothers sample and affected girls sample, respectively. We observed no significant excess of skewed XCI in families with ASD. Interestingly, two mothers and one girl carrying known mutations in X-linked genes (NLGN3, ATRX, MECP2) showed highly skewed XCI, suggesting that ascertainment of XCI could reveal families with X-linked mutations. Linkage analysis was carried out in the subgroup of multiplex families with skewed XCI (≥80:20) and a modest increased allele sharing was obtained in the Xq27-Xq28 region, with a peak Z-score of 1.75 close to rs719489. In summary, our results suggest that there is no major X-linked gene subject to XCI and expressed in blood cells conferring susceptibility to ASD. However, the possibility that rare mutations in X-linked genes could contribute to ASD cannot be excluded. We propose that the XCI profile could be a useful criteria to prioritize families for mutation screening of X-linked candidate genes. © 2008 Wiley-Liss, Inc.

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