Although Blau syndrome has been reported as a genetic disease with high penetrance, asymptomatic carrier cases of a family with the same E383K mutation have also been reported.
Genetic analysis of the patient and his parents, who had no medical past history, revealed heterozygous 1147G>A (E383K) mutation of NOD2 in the patient and in his father, so the patient was diagnosed with Blau syndrome and his father as an asymptomatic carrier.
The objective was to study both ex vivo and in vitro secretion of pro-inflammatory cytokines in patients affected by Blau syndrome (BS) and carrying p.E383K mutation in the CARD15/NOD2 gene associated with the disease.
In an Italian family with BS, we detected a novel mutation E383K, whose pathogenicity is strongly supported by cosegregation with the disease in the family and absence in controls, and by the evolutionary conservation and structural role of the affected glutamate close to the Walker B motif of the nucleotide-binding site in the NACHT domain.