Phenotype–Genotype Analysis of Cryopyrin-Associated Periodic Syndromes (CAPS): Description of a Rare Non-Exon 3 and a Novel CIAS1 Missense Mutation

  • Adriana A. Jesus
  • Clovis A. Silva
  • Gesmar R. Segundo
  • Ivona Aksentijevich
  • Erika Fujihira
  • Mônica Watanabe
  • Magda Carneiro-Sampaio
  • Alberto J. S. Duarte
  • João B. Oliveira
Article

Abstract

We describe in this paper the phenotype–genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3.

Keywords

Cryopyrin periodic fever NOMID CINCA CIAS1 

References

  1. 1.
    Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 2005;17:586–99.PubMedCrossRefGoogle Scholar
  2. 2.
    Hull KM, Shoham N, Chae JJ, Aksentijevich I, Kastner DL. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol 2003;15:61–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Masters SL, Lobito AA, Chae J, Kastner DL. Recent advances in the molecular pathogenesis of hereditary recurrent fevers. Curr Opin Allergy Clin Immunol 2006;6:428–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J, Kolodner RD et al. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum 2007;56:1273–85.PubMedCrossRefGoogle Scholar
  5. 5.
    Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum 2002;46:3340–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Ting JP, Kastner DL, Hoffman HM. CATERPILLERs, pyrin and hereditary immunological disorders. Nat Rev Immunol 2006;6:183–95.PubMedCrossRefGoogle Scholar
  7. 7.
    Neven B, Callebaut I, Prieur AM, Feldmann J, Bodemer C, Lepore L et al. Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU. Blood 2004;103:2809–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Matsubayashi T, Sugiura H, Arai T, Oh-Ishi T, Inamo Y. Anakinra therapy for CINCA syndrome with a novel mutation in exon 4 of the CIAS1 gene. Acta Paediatr 2006;95:246–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Martinon F, Tschopp J. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 2004;117:561–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Simon A, van der Meer JW. Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am J Physiol Regul Integr Comp Physiol 2007;292:R86–R98.PubMedGoogle Scholar
  11. 11.
    Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet 2004;364:1779–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Rynne M, Maclean C, Bybee A, McDermott MF, Emery P. Hearing improvement in a patient with variant Muckle–Wells syndrome in response to interleukin 1 receptor antagonism. Ann Rheum Dis 2006;65:533–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 2006;355:581–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Adriana A. Jesus
    • 1
  • Clovis A. Silva
    • 1
  • Gesmar R. Segundo
    • 3
  • Ivona Aksentijevich
    • 4
  • Erika Fujihira
    • 5
  • Mônica Watanabe
    • 5
  • Magda Carneiro-Sampaio
    • 2
  • Alberto J. S. Duarte
    • 6
  • João B. Oliveira
    • 5
    • 6
  1. 1.Pediatric Rheumatology UnitUniversity of São PauloSão PauloBrazil
  2. 2.Pediatrics DepartmentUniversity of São PauloSão PauloBrazil
  3. 3.Federal University of UberlandiaUberlandiaBrazil
  4. 4.Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIHBethesdaUSA
  5. 5.Molecular Immunology and Genetics Section, Laboratory of Medical Investigation #56, Department of DermatologyUniversity of São PauloSão PauloBrazil
  6. 6.Research InstituteHospital do CoraçãoSão PauloBrazil

Personalised recommendations