A Novel NOD2-associated Mutation and Variant Blau Syndrome: Phenotype and Molecular Analysis.

PURPOSE: To describe the clinical and molecular implications of a novel mutation in the NOD2/CARD15 gene on a family and its seven affected members.

METHODS

We reviewed the clinical presentations of family members who came to our center for refractory uveitis. Genetic testing and molecular testing was performed.

RESULTS

All affected members had adult onset recurrent non-granulomatous panuveitis. The inheritance pattern suggested an autosomal dominant disease and genetic analysis identified a novel mutation in the NOD2 gene that converted amino acid 600 from glutamate to alanine (E600A). Transfection of the E600A NOD2 into human embryonic kidney-293 (HEK293) cells revealed constitutive activation and a reduced ability to respond to the NOD2 ligand, muramyl dipeptide (MDP) as compared with wild-type NOD2.

CONCLUSIONS

The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement.