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Mutations in autism susceptibility candidate 2 (AUTS2) in patients with mental retardation

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Abstract

We report on three unrelated mentally disabled patients, each carrying a de novo balanced translocation that truncates the autism susceptibility candidate 2 (AUTS2) gene at 7q11.2. One of our patients shows relatively mild mental retardation; the other two display more profound disorders. One patient is also physically disabled, exhibiting urogenital and limb malformations in addition to severe mental retardation. The function of AUTS2 is presently unknown, but it has been shown to be disrupted in monozygotic twins with autism and mental retardation, both carrying a translocation t(7;20)(q11.2;p11.2) (de la Barra et al. in Rev Chil Pediatr 57:549–554, 1986; Sultana et al. in Genomics 80:129–134, 2002). Given the overlap of this autism/mental retardation (MR) phenotype and the MR-associated disorders in our patients, together with the fact that mapping of the additional autosomal breakpoints involved did not disclose obvious candidate disease genes, we ascertain with this study that AUTS2 mutations are clearly linked to autosomal dominant mental retardation.

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Acknowledgements

We sincerely thank the patients and parents for participation in this study; R. Wegner and H. Neitzel for establishing the karyotype of patient 2; S. Freier and H. Madle for help with cell culture; P. Viertel and M. Schubert for technical assistance; W. Chen for help with LCR analysis; C. Hultschig for spotting the slides; Pieter de Jong and the BACPAC Resources Centre (http://www.bacpac.chori.org/) for providing DNA and clones of the human “32k” BAC re-array set, Nigel Carter and the Mapping Core and Map Finishing groups of the Wellcome Trust Sanger Institute for initial clone supply of the 1 Mb Sanger set and the COST B19 Action “Molecular Cytogenetics of Solid Tumours” for the assembly of the subtelomeric clone set. This work was supported by the National Genome Research Network (NGFN, project numbers 01GR0105 and 01GR0414). The Wilhelm Johannsen Centre for Functional Genome Research was established by the Danish National Research Foundation.

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Authors and Affiliations

  1. Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, 14195, Berlin, Germany

    Vera M. Kalscheuer, Andreas Tzschach, Sarah A. Shoichet, Corinna Menzel, Fikret Erdogan, Hans-Hilger Ropers & Reinhard Ullmann

  2. Clinical Genetics Department and MRC Human Genetics Unit, MRC, Western General Hospital, Edinburgh, UK

    David FitzPatrick

  3. Wilhelm Johannsen Centre for Functional Genome Research, The Panum Institute, Copenhagen, Denmark

    Niels Tommerup & Merete Bugge

  4. Department of Medical Biochemistry and Genetics, The Panum Institute, Copenhagen, Denmark

    Niels Tommerup & Erik Niebuhr

  5. Institute for Human Genetics, Charité Campus Virchow-Klinikum, Berlin, Germany

    Luitgard M. Neumann

  6. Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

    Ger Arkesteijn

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  1. Vera M. Kalscheuer
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  2. David FitzPatrick
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Correspondence to Vera M. Kalscheuer.

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Kalscheuer, V.M., FitzPatrick, D., Tommerup, N. et al. Mutations in autism susceptibility candidate 2 (AUTS2) in patients with mental retardation. Hum Genet 121, 501–509 (2007). https://doi.org/10.1007/s00439-006-0284-0

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  • DOI: https://doi.org/10.1007/s00439-006-0284-0

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