Nazanin Ebrahimiadib1,2, Khawla Abu Samra1,2, Aaron M Domina3, Ethan R Stiles3, Roger Ewer3, Charlie P Bocian3, C Stephen Foster1,2,4. 1. a Massachusetts Eye Research and Surgery Institution , Waltham , MA , USA. 2. b Ocular Immunology and Uveitis Foundation , Waltham , MA , USA. 3. c Husson University School of Pharmacy , Bangor , Maine , USA. 4. d Harvard Medical School, Department of Ophthalmology , Boston , Massachusetts , 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.
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.
Authors: Zuzana Parackova; Marketa Bloomfield; Petra Vrabcova; Irena Zentsova; Adam Klocperk; Tomas Milota; Michael Svaton; Jean-Laurent Casanova; Jacinta Bustamante; Eva Fronkova; Anna Sediva Journal: J Clin Immunol Date: 2019-11-23 Impact factor: 8.542