Document Detail

Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis.
MedLine Citation:
PMID:  19116920     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Blau syndrome and its sporadic counterpart, early-onset sarcoidosis (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and uveitis. This systemic inflammatory granulomatosis is associated with mutations in the NOD2 gene. The aim of this study was to describe the clinical manifestations of Blau syndrome/EOS in Japanese patients and to determine whether the NOD2 genotype and its associated basal NF-kappaB activity predict the Blau syndrome/EOS clinical phenotype. METHODS: Twenty Japanese patients with Blau syndrome/EOS and NOD2 mutations were recruited. Mutated NOD2 was categorized based on its basal NF-kappaB activity, which was defined as the ratio of NF-kappaB activity without a NOD2 ligand, muramyldipeptide, to NF-kappaB activity with muramyldipeptide. RESULTS: All 9 mutations, including E383G, a novel mutation that was identified in 20 patients with Blau syndrome/EOS, were detected in the centrally located NOD region and were associated with ligand-independent NF-kappaB activation. The median age of the patients at disease onset was 14 months, although in 2 patients in Blau syndrome families (with mutations R334W and E383G, respectively) the age at onset was 5 years or older. Most patients with Blau syndrome/EOS had the triad of skin, joint, and ocular symptoms, the onset of which was in this order. Clinical manifestations varied even among familial cases and patients with the same mutations. There was no clear relationship between the clinical phenotype and basal NF-kappaB activity due to mutated NOD2. However, when attention was focused on the 2 most frequent mutations, R334W and R334Q, R334W tended to cause more obvious visual impairment. CONCLUSION: NOD2 genotyping may help predict disease progression in patients with Blau syndrome/EOS.
Ikuo Okafuji; Ryuta Nishikomori; Nobuo Kanazawa; Naotomo Kambe; Akihiro Fujisawa; Shin Yamazaki; Megumu Saito; Takakazu Yoshioka; Tomoki Kawai; Hidemasa Sakai; Hideaki Tanizaki; Toshio Heike; Yoshiki Miyachi; Tatsutoshi Nakahata
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  60     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-03-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-50     Citation Subset:  AIM; IM    
Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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MeSH Terms
Age of Onset
Arthritis / genetics*,  physiopathology
Disease Progression
Middle Aged
NF-kappa B / metabolism
Nod2 Signaling Adaptor Protein / genetics*
Point Mutation
Predictive Value of Tests
Sarcoidosis / genetics*,  physiopathology
Skin Diseases / genetics*,  physiopathology
Uveitis / genetics*,  physiopathology
Vision, Low / genetics,  physiopathology
Young Adult
Reg. No./Substance:
0/NF-kappa B; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein

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