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 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.
Bennett
C L
CL
Department of Pediatrics, University of Washington School of Medicine, Seattle, USA.
Yoshioka
R
R
Kiyosawa
H
H
Barker
D F
DF
Fain
P R
PR
Shigeoka
A O
AO
Chance
P F
PF
D000328:Adult; D015152:Blotting, Northern; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D018387:Codon, Initiator / Q000235:genetics; D004252:DNA Mutational Analysis; D003967:Diarrhea / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013577:Syndrome; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000503:physiopathology; D051316:Wiskott-Aldrich Syndrome Protein; D014960:X Chromosome / Q000235:genetics*
D018387:Codon, Initiator; D011506:Proteins; D012333:RNA, Messenger; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein