Background Blau Syndrome is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Polymorphisms in the leucine-rich repeats (LRR) of CARD15 are associated with Crohn's Disease, and mutations in the NBD domain are observed in Blau syndrome (3).
Objectives We describe two patients with granulomatous uveitis carrying rare genetic variants of NOD2.
Methods The analysis of the coding exons of the NOD2/CARD15 gene was performed in our two patients because they had a granulomatous uveitis.
Results The first patient, a 14 years old boy, had an isolated bilateral granulomatous uveitis since he was 10 years old. He was treated by steroids and methotrexate. He carried the A725G variant of NOD2 (rs5743278 MAF 0.018). The second patient, a 15 years old girl had an isolated bilateral granulomatous panuveitis since she was 5 years old. She was treated by azathioprine and steroids. She carried two other rare genetic variants of NOD2: H287Y and L682F (MAF=0.0002).
Conclusions NOD2 is composed of three domains: a C-terminal LRR domain involved in ligand recognition, a central NBD and an N-terminal CARD domain. Our two patients carried a rare genetic variant located between the LRR and the NBD domains (A725G and L682F). The A725G variant has been previously described in patients with Crohn disease's (CD) phenotype by Hugot et al (3) but our first patient had no clinical symptom related to CD. The second patient carried another rare variant located in the NBD domain (H287Y), compatible with the diagnosis of Blau syndrome. According to these observations, genetic variations located between the LRR and the NBD domains of NOD2 might be associated with the occurrence of granulomatous uveitis. It should be thus recommended to screen NOD2 mutations in patients with isolated granulomatous uveitis.
Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689–93. PubMed PMID: 4056967. Epub 1985/11/01. eng.
Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19–20. PubMed PMID: 11528384. Epub 2001/08/31. eng.
Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599–603. PubMed PMID: 11385576. Epub 2001/06/01. eng.
Disclosure of Interest None declared