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NOD2-associated autoinflammatory disease: a large cohort study
被引:49
作者:

Yao, Qingping
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机构:
Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA

Shen, Min
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Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA

McDonald, Christine
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机构:
Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA

Lacbawan, Felicitas
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机构:
Cleveland Clin, Dept Mol Pathol, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA

Moran, Rocio
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机构:
Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA

Shen, Bo
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h-index: 0
机构:
Cleveland Clin, Dept Gastroenterol Hepatol, Cleveland, OH 44106 USA Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA
机构:
[1] Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA
[2] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44106 USA
[3] Cleveland Clin, Dept Mol Pathol, Cleveland, OH 44106 USA
[4] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA
[5] Cleveland Clin, Dept Gastroenterol Hepatol, Cleveland, OH 44106 USA
关键词:
nucleotide-binding oligomerization domain containing 2 (NOD2);
NOD2-associated autoinflammatory disease;
Crohn's disease;
IVS8(+158);
INFLAMMATORY-BOWEL-DISEASE;
NF-KAPPA-B;
CROHNS-DISEASE;
SUSCEPTIBILITY GENE;
CARD15;
MUTATIONS;
BLAU-SYNDROME;
NOD2;
PHENOTYPE;
ASSOCIATION;
ASHKENAZI;
D O I:
10.1093/rheumatology/kev207
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Objective. The aims of the study were to characterize the genotype profile of nucleotide-binding oligomerization domain containing 2 (NOD2)-associated autoinflammatory disease (NAID) and to report an extended study of the disease. Methods. A total of 143 adult patients presented with clinical phenotypes suspicious for NAID and all were genotyped for NOD2 sequence variants. The genotype frequencies were compared between our cohort and literature reports. These patients were divided into two groups predicated on the presence or absence of NOD2 variants. Results. Of the 143 patients, 67 (47%) carry NOD2 variants; the genotype frequency was significantly higher among our cohort than in the historical healthy controls. Fifty-four of the 67 carriers of NOD2 variants had NAID, which has a genotype profile that is somewhat different from Crohn's disease. All NAID patients were non-Jewish whites and 69% were women. The median age at onset was 33.5 years and the median disease duration at diagnosis was 10.7 years. NAID was sporadic in 93% of cases. Patients typically presented with periodic fever, dermatitis and inflammatory arthritis. As compared with the NOD2 variant-negative patients, the skin disease more typically manifested as erythematous patches or plaques on the trunk. Oligopolyarthritis/-arthralgia was common, with characteristic distal lower extremity swelling. Associated NOD2 variants were primarily IVS8(+158) or compound IVS8(+158) and R702W. Conclusion. This study underscores the NOD2 genotype association with NAID, which is a genetically complex multisystem disorder. It differs phenotypically from Crohn's disease with a distinct genotype profile. This disease may be more common than initially thought.
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页码:1904 / 1912
页数:9
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Zouali, H
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Cézard, JP
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Colombel, JF
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Belaiche, J
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Almer, S
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Tysk, C
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

O'Morain, C
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Gassull, M
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Binder, V
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Finkel, Y
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Modigliani, R
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Gower-Rousseau, C
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Macry, J
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Merlin, F
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Chamaillard, M
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Jannot, AS
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Thomas, G
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France

Hugot, JP
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机构: Fdn Jean Dausset, CEPH, F-75010 Paris, France