Blau syndrome associated with a CARD15/NOD2 mutation

PURPOSE: To report a new family with Blau syndrome caused by CARD15/NOD2 mutation. DESIGN: Observational case series. METHODS: Detailed clinical evaluation in three affected relatives with Blau syndrome. Haplotype and mutation analysis of the CARD15/NOD2 gene were performed. RESULTS: Ocular manifestations identified in the proband include bilateral band keratopathy, cataract, iritis, vitritis and severe granulomatous choroidopathy. The mother and one brother of the proband exhibit the same characteristic organ involvements of this disease. Haplotype analysis from the pericentromeric region on chromosome 16 identified a common haplotype in all affected relatives that is absent in unaffected relatives. Sequencing analysis revealed a heterozygous pathogenic mutation in the CARD15/NOD2 gene, the previously reported p.R334W substitution. CONCLUSION: Blau syndrome is a rare autosomal,dominant disease that can lead to severe visual impairment. The search of a CARD15/NOD2 mutation could be helpful in the differential diagnosis of childhood uveitis.