Two novel members of the interleukin-1 receptor gene family, one deleted in Xp22.1-Xp21.3 mental retardation

Eur J Hum Genet. 2000 Feb;8(2):87-94. doi: 10.1038/sj.ejhg.5200415.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adolescent
  • Amino Acid Sequence
  • Child
  • Chromosome Deletion
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Dystrophin / genetics
  • Family Health
  • Humans
  • Intellectual Disability / genetics*
  • Interleukin-1 Receptor Accessory Protein
  • Male
  • Molecular Sequence Data
  • Multigene Family
  • Phylogeny
  • RNA / genetics
  • Receptors, Interleukin-1 / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Sex Chromosome Aberrations
  • X Chromosome / genetics*


  • 5' Untranslated Regions
  • DNA, Complementary
  • Dystrophin
  • IL1RAPL1 protein, human
  • IL1RAPL2 protein, human
  • Interleukin-1 Receptor Accessory Protein
  • Receptors, Interleukin-1
  • RNA

Associated data

  • GENBANK/AF181284
  • GENBANK/AF181285
  • GENBANK/AF181286