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Dominant mutations in the CIAS1 gene cause a spectrum of autoinflammatory diseases such as familial cold autoinflammatory syndrome, FCAS, which is characterized by episodes of urticaria, arthralgia, fever and conjunctivitis after generalized exposure to cold. We here describe patients of two German families with the 592G-->A, V198M mutation, which has been described to induce FCAS before. However, in our patients the clinical phenotype was very different from this disease. They never had urticaria, cold induced fever or conjunctivitis; instead the following symptoms occurred: Very regular periodic fever, irregular severe febrile episodes, relatively mild arthralgia, dry cough, cardiomyopathy, nephropathy and euthyroid thyroiditis all being reversible. We conclude that the clinical phenotype associated with mutations in the CIAS1 gene is much broader than assumed before.

In an adult patient suffering from X‐linked chronic granulomatous disease (X‐CGD) with residual activity of the NADPH–oxidase we found an unusual biochemical constellation with a defective gp91‐phox gene. As shown by Western blot using a specific antibody the gp91‐phox protein was normal in PMN. However, NADPH–oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91‐phox gene was excluded. Sequencing of the gp91‐phox cDNA revealed an in‐frame deletion of a TTC triplet in exon VI of the gp91‐phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91‐phox protein. Sequencing of genomic DNA from the heterozygous daughter of the propositus confirmed this mutation. The absence of a functional cytochrome b558‐spectrum in granulocytes of the patient suggests an involvement of the phenylalanine 216 area in heme binding by gp91‐phox. This is the first mutation described in a X‐CGD patient with absence of a functional cytochrome b558‐spectrum but with detectable gp91‐phox protein and residual NADPH‐oxidase activity.