title: NLRP3 A439V Mutation in a Large Family with Cryopyrin-associated Periodic Syndrome: Description of Ophthalmologic Symptoms in Correlation with Other Organ Symptoms.
abstract: Cryopyrin-associated periodic syndrome (CAPS) is a group of inherited autoinflammatory disorders caused by mutations in the NLRP3 gene resulting in the overproduction of interleukin 1β. NLRP3 mutations cause a broad clinical phenotype of CAPS. The aims of the study were to evaluate clinical, laboratory, and genetic features of a 5-generation family with CAPS focusing in detail on ocular symptoms.
  
  
  
  In a retrospective observational cohort study, consecutive family members were screened for the presence of the NLRP3 mutation. Patients underwent standardized clinical, laboratory, and ophthalmological assessments. The genotype-specific risk of ophthalmological findings and other organ symptoms was determined.
  
  
  
  Twenty-nine patients were clinically affected. The A439V mutation encoded by exon 3 of the NLRP3 gene was found in 15 of 37 family members (41%). The most common clinical features were musculoskeletal symptoms, headaches, and ophthalmological symptoms. The mutation-positive patients were characterized by more frequent skin rashes, ocular symptoms, arthralgia, arthritis, and severe Muckle-Wells syndrome (MWS) Disease Activity Score. Rosacea was diagnosed in 8 patients.
  
  
  
  The NLRP3 mutation A439V is associated with a heterogeneous clinical spectrum of familial cold autoinflammatory syndrome/MWS-overlap syndrome. Skin rash and eye diseases, such as conjunctivitis and uveitis, were positively correlated with this mutation.
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors. Bianka.sob@gmx.de.
authors.forename: Bianka
authors.initials: B
authors.lastname: Sobolewska
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
authors.forename: Eva
authors.initials: E
authors.lastname: Angermair
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
authors.forename: Christoph
authors.initials: C
authors.lastname: Deuter
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
authors.forename: Deshka
authors.initials: D
authors.lastname: Doycheva
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Kuemmerle-Deschner
authors.affiliation: From the Center for Ophthalmology, and the Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen, Tuebingen, Germany.B. Sobolewska, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; E. Angermair, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; C. Deuter, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; D. Doycheva, MD, Center for Ophthalmology, Eberhard-Karls University Tuebingen; J. Kuemmerle-Deschner, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Eberhard-Karls University Tuebingen; M. Zierhut, MD, PhD, Center for Ophthalmology, Eberhard-Karls University Tuebingen. Dr. Kuemmerle-Deschner and Dr. Zierhut contributed equally to this report and should be considered as co-senior authors.
authors.forename: Manfred
authors.initials: M
authors.lastname: Zierhut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018771:Arthralgia / Q000209:etiology / Q000235:genetics; D001168:Arthritis / Q000209:etiology / Q000235:genetics; D002648:Child; D003231:Conjunctivitis / Q000209:etiology* / Q000235:genetics; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D014605:Uveitis / Q000209:etiology* / Q000235:genetics; D055815:Young Adult
chemical_list: D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: FAMILIAL COLD AUTOINFLAMMATORY SYNDROME; MUCKLE-WELLS SYNDROME; NLRP3 MUTATION; ROSACEA; UVEITIS