X-Linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23-Xq13.3

Am J Hum Genet. 2000 Feb;66(2):461-8. doi: 10.1086/302761.


We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequently results in death during infancy or childhood. Linkage analysis mapped the XPID gene to a 17-cM interval defined by markers DXS8083 and DXS8107 on the X chromosome, at Xp11. 23-Xq13.3. The maximum LOD score was 3.99 (recombination fraction0) at DXS1235. Because this interval also harbors the gene for Wiskott-Aldrich syndrome (WAS), we investigated mutations in the WASP gene, as the molecular basis of XPID. Northern blot analysis detected the same relative amount and the same-sized WASP message in patients with XPID and in a control. Analysis of the WASP coding sequence, an alternate promoter, and an untranslated upstream first exon was carried out, and no mutations were found in patients with XPID. A C-->T transition within the alternate translation start site cosegregated with the XPID phenotype in this family; however, the same transition site was detected in a normal control male. We conclude that XPID maps to Xp11.23-Xq13.3 and that mutations of WASP are not associated with XPID.

MeSH terms

  • Adult
  • Blotting, Northern
  • Child
  • Child, Preschool
  • Chromosome Mapping*
  • Codon, Initiator / genetics
  • DNA Mutational Analysis
  • Diarrhea / genetics*
  • Diarrhea / physiopathology
  • Exons / genetics
  • Female
  • Humans
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Phenotype
  • Polyendocrinopathies, Autoimmune / genetics*
  • Polyendocrinopathies, Autoimmune / immunology*
  • Promoter Regions, Genetic / genetics
  • Proteins / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Syndrome
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome / physiopathology
  • Wiskott-Aldrich Syndrome Protein
  • X Chromosome / genetics*


  • Codon, Initiator
  • Proteins
  • RNA, Messenger
  • WAS protein, human
  • Wiskott-Aldrich Syndrome Protein

Associated data

  • GENBANK/AF115548
  • GENBANK/AF115549