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A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation

Nature Genetics volume 23, pages 25–31 (1999)Cite this article

Abstract

We demonstrate here the importance of interleukin signalling pathways in cognitive function and the normal physiology of the CNS. Thorough investigation of an MRX critical region in Xp22.1–21.3 enabled us to identify a new gene expressed in brain that is responsible for a non-specific form of X-linked mental retardation. This gene encodes a 696 amino acid protein that has homology to IL-1 receptor accessory proteins. Non-overlapping deletions and a nonsense mutation in this gene were identified in patients with cognitive impairment only. Its high level of expression in post-natal brain structures involved in the hippocampal memory system suggests a specialized role for this new gene in the physiological processes underlying memory and learning abilities.

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Figure 1: Physical map of the MRX34 deletion in Xp22.1–p21.3 and genomic structure of IL1RAPL.
Figure 2: Evidence that the critical genomic region contains a candidate gene.
Figure 3: Predicted protein sequences and genomic organization of IL1RAPL .
Figure 4: Mutations in IL1RAPL.
Figure 5: Expression of Il1rapl.

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Acknowledgements

We thank patients and family members for participation; F. Francis, V. des Portes and M. Catala for helpful discussions; F. Fauchereau, G. Friocourt and P. Chaffey for their contributions; and the Sanger Centre and Baylor College of Medicine for making available PAC and BAC sequencing data. This work was supported in part by grants from INSERM, including an APEX program number 4X007E, the Association Française contre les Myopathies and The Fondation Jérôme Lejeune.

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Authors and Affiliations

  1. INSERM Unité 129–ICGM, CHU Cochin, 24 Rue du Faubourg Saint Jacques, Paris, 75014, France

    Alain Carrié, Thierry Bienvenu, Marie-Claude Vinet, Nathalie McDonell, Philippe Couvert, Ramzi Zemni, Axel Kahn, Cherif Beldjord & Jamel Chelly

  2. The Flanders Interuniversity Institute for Biotechnology, UZ Gasthuisberg, Herestraat 49, Leuven, B-3000, Belgium

    Lin Jun, Suzanna Frints & Peter Marynen

  3. Laboratoire de Technologies Cellulaires, Institut Pasteur, 25 rue du Dr Roux, 75724 cedex 15, Paris, France

    Ana Cardona

  4. Center for Human Genetics, Clinical Genetics University, UZ Gasthuisberg, Herestraat 49, Leuven, B-3000, Belgium

    Griet Van Buggenhout, Suzanna Frints & Jean-Pierre Fryns

  5. 417 Department of Human Genetics, University Hospital Nijmegen, Geert Grooteplein 10, Nijmegen, 6500 HB, The Netherlands

    Griet Van Buggenhout & Ben Hamel

  6. Centre Hospitalier de Tours, Service de Génétique, Hopital Bretonneau, 2 Boulevard Tonnelle, 37044 Cedex, Tours, France

    Claude Moraine

  7. Max-Plank-Institute for Molecular Genetics, Ihnestrasse 73, Berlin-Dahlem, Germany

    Hans H. Ropers

  8. Abteilung Medizinische Genetik, Goethestr. 29, München, 80336, Germany

    Tim Strom

  9. The Sanger Centre, Wellcome Trust Genome Campus, Cambridge, Hinxton, UK

    Gareth R. Howell, Adam Whittaker & Mark T. Ross

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  1. Alain Carrié
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Correspondence to Jamel Chelly.

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Carrié, A., Jun, L., Bienvenu, T. et al. A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Nat Genet 23, 25–31 (1999). https://doi.org/10.1038/12623

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