Min Shen1, Rocio Moran2, Kenneth J Tomecki3, Qingping Yao4. 1. Department of Rheumatic and Immunologic Disease/A50, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. 2. Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH. 3. Dermatology, Cleveland Clinic, Cleveland, OH. 4. 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.
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.
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.