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A Novel NOD2-associated Mutation and Variant Blau Syndrome: Phenotype and Molecular Analysis |
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| Authors: | Nazanin Ebrahimiadib Khawla Abu Samra Aaron M Domina Ethan R Stiles Roger Ewer Charlie P Bocian |
| Institution: | 1. Massachusetts Eye Research and Surgery Institution, Waltham, MA, USA;2. Ocular Immunology and Uveitis Foundation, Waltham, MA, USA;3. Husson University School of Pharmacy, Bangor, Maine, USA |
| Abstract: | 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. |
| Keywords: | Arthritis Blau syndrome dermatitis early onset sarcoidosis NOD2 associated auto-inflammatory disorder NOD2/CARD15 uveitis |