X-Linked Syndrome of Polyendocrinopathy, Immune Dysfunction, and Diarrhea Maps to Xp11.23-Xq13.3

Abstract

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.

Genetic control of autoimmunity in Type I diabetes and associated disorders

“…T lymphocytes in these patients have a cytokine profile markedly skewed toward a Th2 phenotype (high concentration of IL-4, IL-5 and IL-13, low concentration of IFN-gamma) [173,174]. Several mutations in JM2, a gene in the pericentromeric region of the X chromosome (Xp11.23-Xq13.3) have been described in patients with XPID [175,173,176] (Fig. 5).…”

“…5). This interval also harbours the gene for Wiskott Aldrich syndrome but mutations in the Wiskott Aldrich protein (WASP) gene have not been found in patients with XPID [175,177]. The predicted wild-type protein, named scurfin or Foxp3, contains a winged helix [fork head homology domain (FKH)] motif at the carboxy terminus, a C2H2 zinc finger domain (Zn) and a 3-heptad Zip motif upstream of the FKH, suggesting that this protein functions as a transcription factor.…”

Escape from tolerance in the human X-linked autoimmunity–allergic disregulation syndrome and the Scurfy mouse

“…Many of the affected children have hypogammaglobulinemia with low IgG and IgA levels, but this may be explained by persistent diarrhea with a protein-losing enteropathy. Because of the variability in presentation, this syndrome mapping in each case to the pericentromeric region of the X chromosome (Xp11.23-Xq13.3) has been referred to as X-linked polyendocrinopathy, immune dysfunction, and diarrhea (XPID) and X-linked autoimmunityimmunodeficiency syndrome (XLAID) as well as XLAAD (5,6).…”

Análise da expressão gênica do FOXP3, MIP-3? e Interleucinas 2, 10 e 35 em pacientes com ulceração aftosa recorrente

“…O FOXP3 tem sido considerado um marcador específico de linfócitos T reguladores CD4+CD25 high (Bennett et al, 2000;Beyer;Schultze, 2006;Zhang, Zhao, 2007;Lewkowicz et al, 2008), e seu RNA mensageiro apresentou-se 11.06…”

“…humano está localizado no braço curto do cromossomo X, consiste de 11 éxons e codifica uma proteína de 431 aminoácidos, também denominada FOXP3 (Bennett et al, 2000). Linfócitos Treg possuem capacidade de suprimir a ativação e expansão de linfócitos autorreativos, colaborando para a manutenção da tolerância.…”