title: Granulomatous disease associated with NOD2 sequence variants and familial camptodactyly: An intermediate form of NOD2-associated diseases?
abstract: OBJECTIVE
  Nucleotide-binding oligomerization domain-containing protein-2 (NOD2)-associated diseases may be a spectrum of disease. We report two families who exhibited an intermediate form of Blau syndrome and NOD2-associated autoinflammatory disease (NAID).
  
  
  METHODS
  We identified two families with granulomatous disease. The clinical phenotypes and genotypes of these two families were reviewed and analyzed.
  
  
  RESULTS
  The proband in family 1 was a white 57-year-old woman, with camptodactyly (age 6 years), inflammatory polyarthritis and dermatitis (age of 30 years), and cough, dyspnea, dry eyes, parotid gland enlargement, and fever. A computerized tomography showed mediastinal lymphadenopathy without hilar involvement, and a mediastinal lymph node biopsy revealed non-caseating granuloma. Pedigree analysis suggested autosomal dominant inheritance, and genetic testing identified a NOD2 sequence variant IVS8(+158). The proband in family 2 was a white 50-year-old woman with inflammatory polyarthritis and periarticular subcutaneous nodules. Skin biopsy showed non-necrotizing granuloma. There was a family history of camptodactyly, and genetic testing identified a NOD2 sequence variant R703C.
  
  
  CONCLUSIONS
  Both probands had granulomatous disease and autosomal dominant phenotype of familial camptodactyly coupled with the presence of the NOD2 sequence variants, IVS8(+158), and R703C. Granulomatous disease associated with NOD2 variants may be an intermediate form between Blau syndrome and NAID.
authors.affiliation: Department of Rheumatic and Immunologic Disease/A50, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Rocio
authors.initials: R
authors.lastname: Moran
authors.affiliation: Dermatology, Cleveland Clinic, Cleveland, OH.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Tomecki
authors.affiliation: Department of Rheumatic and Immunologic Disease/A50, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195; Division of Rheumatology, Allergy and Immunology, Stony Brook University, Stony Brook, NY. Electronic address: yaoq@ccf.org.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yao
mesh_terms: D001168:Arthritis / Q000235:genetics; D003872:Dermatitis / Q000235:genetics; D005260:Female; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Blau syndrome; NOD2-associated autoinflammatory disease; Nucleotide-binding oligomerization domain-containing protein-2