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

• Published in: Ocular immunology and inflammation Vol. 26; no. 1; pp. 57 - 64
• Main Authors: Ebrahimiadib, Nazanin, Samra, Khawla Abu, Domina, Aaron M., Stiles, Ethan R., Ewer, Roger, Bocian, Charlie P., Foster, C. Stephen
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.01.2018
• Subjects: Arthritis; Blau syndrome; dermatitis; early onset sarcoidosis; NOD2 associated auto-inflammatory disorder; NOD2/CARD15; uveitis; NOD2/CARD15; NOD2 associated auto-inflammatory disorder; dermatitis; Blau syndrome; Arthritis; uveitis; early onset sarcoidosis
• ISSN: 0927-3948; 1744-5078
• DOI: 10.1080/09273948.2016.1185529

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.