title: Two novel members of the interleukin-1 receptor gene family, one deleted in Xp22.1-Xp21.3 mental retardation.
abstract: X-linked mental retardation is estimated to affect approximately 1 in 600 males. Although numerous genes responsible for syndromic mental retardation have been identified, the study of non-syndromic mental retardation suffers from intrinsic issues of genetic heterogeneity. During the investigation of three brothers with a contiguous gene deletion syndrome of Becker muscular dystrophy, glycerol kinase deficiency, congenital adrenal hypoplasia, and mental retardation, we found their dystrophin gene to be fused tail-to-tail with a gene encoding a novel member of the interleukin-1 receptor family, IL1RAPL1. This gene has a close relative in Xq22, which we call IL1RAPL2. Both IL1RAPL1 and IL1RAPL2 have novel C-terminal sequences not present in other related proteins, and are encoded by very large genes. The 1.8-megabase deletion in these patients removes not only the last exon of the dystrophin gene, the entire glycerol kinase and DAX-1 genes, and the MAGE-B gene cluster, but also three exons encoding the intracellular signalling domain of IL1RAPL1. The literature contains multiple reports of patients with non-syndromic mental retardation in association with an Xp22.1-Xp21.3 microdeletion of a marker which lies within the IL1RAPL1 gene. The gene is also wholly or partially deleted in patients with mental retardation as part of a contiguous deletion syndrome. We suggest that IL1RAPL1, and perhaps IL1RAPL2, are strong candidates for X-linked non-syndromic mental retardation loci, and that molecules resembling IL-1 and IL-18 play a role in the development or function of the central nervous system.
authors.affiliation: Division of Medical & Molecular Genetics, GKT Medical School, Guy's Hospital, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: R J
authors.initials: RJ
authors.lastname: Gardner
authors.forename: R
authors.initials: R
authors.lastname: Viswesvaraiah
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: R G
authors.initials: RG
authors.lastname: Roberts
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002872:Chromosome Deletion; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005192:Family Health; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D053577:Interleukin-1 Receptor Accessory Protein; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012313:RNA / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012729:Sex Chromosome Aberrations; D014960:X Chromosome / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D018076:DNA, Complementary; D016189:Dystrophin; C407643:IL1RAPL1 protein, human; C407644:IL1RAPL2 protein, human; D053577:Interleukin-1 Receptor Accessory Protein; D017472:Receptors, Interleukin-1; D012313:RNA