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

We describe genetic analysis of a large pedigree with an X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea (XPID), which frequ ently results in death during infancy or childhood. Linkage analysis mapped the XPID gene to a 17-cM interval defined by markers DXS8083 and DXS8107 o n the X chromosome, at Xp11.23-Xq13.3. The maximum LOD score was 3.99 (reco mbination fraction0) at DXS1235. Because this interval also harbors the gen e 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 promot er, and an untranslated upstream first exon was carried out, and no mutatio ns were found in patients with XPID. A C-->T transition within the alternat e translation start site cosegregated with the XPID phenotype in this famil y; 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 ar e not associated with XPID.