title: Long-term clinical course of patients carrying the Q703K mutation in the NLRP3 gene: a case series.
abstract: BACKGROUND
  Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of apparently distinct, rare, autosomal dominant autoinflammatory disorders of increasing severity caused by NLRP3 gene mutations. The Q703K allele is a variant of unknown pathogenetic significance, and has been considered to be both a clinically unremarkable polymorphism and a low- penetrance mutation.
  
  
  OBJECTIVE
  To analyse the long-term clinical course in a cohort of patients presenting with periodic fever attacks and carrying the Q703K mutation in the NLRP3 gene.
  
  
  METHODS
  Seven Caucasian patients (mean age 37.3±8.5 years, 2 males and 5 females) were identified as carriers of the Q703K mutation among 71 patients with CAPS-like symptoms.
  
  
  RESULTS
  The mean age at disease onset was 25.58±16.08 years and the mean disease duration was 12.28±8.36. The mean number of febrile episodes was 7.56±6.48 and the mean duration of fever attacks was 6.66±4.71 days. Six out of 7 patients had a low grade fever, while 1 patient had no fever episodes. All patients were characterised by symptoms consistent with recurrent inflammatory syndrome. Six patients out of 7 presented skin lesions, 4/7 arthralgia, 4/7 myalgia, 4/7 conjunctivitis, 3/7 headache. All patients also complained of severe fatigue. In 4/7 patients symptoms were triggered or worsened by generalised cold exposure.
  
  
  CONCLUSIONS
  We suggest that patients carrying the low-penetrance Q703K mutation in the NLRP3 gene may present with FCAS-like symptoms. However, given the high frequency of healthy carriers, the role of additional, still unknown genetic and/or environmental modifiers is conceivable.
authors.affiliation: Interdepartmental Research Centre of Systemic Autoimmune and Autoinflammatory Diseases, Unit of Rheumatology, Policlinico Le Scotte, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitale
authors.forename: Orso Maria
authors.initials: OM
authors.lastname: Lucherini
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Bruno
authors.initials: B
authors.lastname: Frediani
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
mesh_terms: D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D013997:Time Factors; D044465:White People / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human