title: A Novel NOD2-associated Mutation and Variant Blau Syndrome: Phenotype and Molecular Analysis.
abstract: OBJECTIVE
  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.affiliation: a Massachusetts Eye Research and Surgery Institution , Waltham , MA , USA.|b Ocular Immunology and Uveitis Foundation , Waltham , MA , USA.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Ebrahimiadib
authors.affiliation: a Massachusetts Eye Research and Surgery Institution , Waltham , MA , USA.|b Ocular Immunology and Uveitis Foundation , Waltham , MA , USA.
authors.forename: Khawla Abu
authors.initials: KA
authors.lastname: Samra
authors.affiliation: c Husson University School of Pharmacy , Bangor , Maine , USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Domina
authors.affiliation: c Husson University School of Pharmacy , Bangor , Maine , USA.
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Stiles
authors.affiliation: c Husson University School of Pharmacy , Bangor , Maine , USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Ewer
authors.affiliation: c Husson University School of Pharmacy , Bangor , Maine , USA.
authors.forename: Charlie P
authors.initials: CP
authors.lastname: Bocian
authors.affiliation: a Massachusetts Eye Research and Surgery Institution , Waltham , MA , USA.|b Ocular Immunology and Uveitis Foundation , Waltham , MA , USA.|d Harvard Medical School, Department of Ophthalmology , Boston , Massachusetts , USA.
authors.forename: C Stephen
authors.initials: CS
authors.lastname: Foster
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001168:Arthritis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D005451:Fluorescein Angiography; D005938:Glucocorticoids / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008269:Macular Edema / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D009902:Optic Neuritis / Q000175:diagnosis; D010641:Phenotype; D012173:Retinitis / Q000175:diagnosis; D012507:Sarcoidosis; D015423:Scleritis / Q000175:diagnosis; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014162:Transfection; D014605:Uveitis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult; D056660:Hereditary Autoinflammatory Diseases
chemical_list: D020533:Angiogenesis Inhibitors; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: Arthritis; Blau syndrome; NOD2 associated auto-inflammatory disorder; NOD2/CARD15; dermatitis; early onset sarcoidosis; uveitis