STAT1-dependent immunity. The other three mutations affect the SH2 domain. The M654K and K673R mutations impair the tyrosine phosphorylation of STAT1, whereas the K637E mutation impairs both STAT1 phosphorylation and GAF-DNA binding. 16,17 These mutations are loss-offunction or hypomorphic and have been shown to exert a dominant-negative effect on wild-type STAT1 for IFN-γ responses.14,15 We report here the molecular and clinical features of a multiplex kindred with MSMD due to a new STAT1 allele, with a mutation of the tyrosine 701 codon. Methods Case reportThe patient (P1) is a 5-year old Japanese boy born to a non-consanguineous family ( Figure 1B). At the age of 2 months he presented with a mild fever and rash. Initial laboratory tests demonstrated leukocytosis (28.9x10 9 /L) with eosinophilia (11.1x10 9

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Summary CD4+ 25+ regulatory T cells (Tregs) play a role in controlling the development and progression of autoimmunity. The transcription factors Foxp3 and NFATC2 (NFAT1) play key roles in regulating the development and function of Tregs. The present study examined the involvement of Tregs in the pathophysiology of autoimmune neutropenia in children. Tregs were analysed by flow cytometry, based on the expressions of CD4, CD25, and intracellular Foxp3. The expressions of FOXP3 and NFATC2 mRNA in the CD4+ 25+ cells were determined by quantitative real‐time polymerase chain reaction. The percentage of CD4+ 25high Tregs in patients with autoimmune neutropenia was significantly lower than that in age‐matched healthy subjects. The intracellular expression of Foxp3 of CD4+ 25+ cells in patients similarly decreased in comparison to that in healthy subjects. The expression of FOXP3 and NFATC2 mRNA of CD4+ 25+ cells in patients also significantly decreased in comparison to that in healthy subjects. These results suggest that the deficiency of Tregs might thus play an important role in the immunopathophysiology of autoimmune neutropenia in children.

SummaryaIIbb3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause Glanzmann thrombasthenia. This is usually autosomal recessive, while other mutations are known to cause dominantly inherited macrothrombocytopenia (although such cases are rare). Here, we report a 4-generation pedigree including 10 individuals affected by dominantly inherited thrombocytopenia with anisocytosis. Six individuals, whose detailed clinical and laboratory data were available, carried a non-synonymous ITGB3 gene alteration resulting in mutated integrin b3 (ITGB3)-L718P. This mutation causes partial activation of the aIIbb3 complex, which promotes the generation of abnormal pro-platelet-like protrusions through downregulating RhoA (RHOA) activity in transfected Chinese Hamster Ovary cells. These findings suggest a model whereby the integrin b3-L718P mutation contributes to thrombocytopenia through gain-of-function mechanisms.

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