A truncating mutation in the IL1RAPL1 gene is responsible for X-linked mental retardation in the MRX21 family

Elisabetta Tabolacci, M. Grazia Pomponi, Roberta Pietrobono, Alessandra Terracciano, Pietro Chiurazzi, Giovanni Neri

Research output: Contribution to journalArticlepeer-review


X-linked mental retardation (XLMR) is a genetically heterogeneous condition, due to mutations in at least 50 genes, involved in functioning of the central nervous system and located on the X chromosome. Nonspecific XLMR (MRX) is characterized essentially by mental retardation transmitted by X-linked inheritance. More than 80 extended MRX pedigrees have been reported to date, which have been distinguished exclusively by physical position of the corresponding gene on the X chromosome, established by linkage analysis. One such family, MRX21, which was described by us in 1993 and localized to Xp11.4-pter, has now been reanalyzed with additional markers and after one more affected individual had became available. This extra information allowed a significant reduction of the linkage interval and, eventually, identification of the mutant gene. A stop mutation in exon 10 of the IL1RAPL1 gene (in Xp21) was found in the four affected males and in obligate carriers, allowing conclusive counseling of other family members of uncertain carrier status. The W487X mutation results in the production of a truncated IL1RAPL protein, comprised of the extracellular Ig-like domain and transmembrane tract, but lacking the last 210 aminoacids of the cytoplasmic domain. MRX21 is the first extended MRX family with a point mutation in IL1RAPL1 and the second with a stop mutation, which had been previously found only in a small family. Our report confirms the role of the IL1RAPL1 gene in causing nonspecific mental retardation in males and underlines the importance of detailed linkage analysis before candidate gene mutational screening.

Original languageEnglish
Pages (from-to)482-487
Number of pages6
JournalAmerican Journal of Medical Genetics
Volume140 A
Issue number5
Publication statusPublished - Mar 1 2006


  • IL1RAPL1 gene
  • Linkage analysis
  • MRX21
  • Stop mutation
  • X-linked mental retardation

ASJC Scopus subject areas

  • Genetics(clinical)


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