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

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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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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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Correspondence to Jamel Chelly.

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