Article Text

AB1115 A novel mutation in the CIAS1/NLRP3 gene associated with an unexpected phenotype of caps
  1. A. Insalaco1,
  2. P.S. Buonuomo1,
  3. I. Ceccherini2,
  4. C. Bracaglia1,
  5. M. Pardeo1,
  6. R. Nicolai1,
  7. F. De Benedetti1
  1. 1Rheumatology, Department of Pediatric Medicine, Ospedale Pediatrico “Bambino Gesù”, Rome
  2. 2Molecular Genetic Laboratory, Istituto “G. Gaslini”, Genova, Italy


Background Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by heterozygous mutations of CIAS1/NLRP3 gene. Affected patients may present three different phenotypes: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and CINCA syndrome. Common symptoms include sporadic or cold-induced non pruritic urticarial rash and fever. Severe cases suffers from deafness, meningitis, articular contracture and secondary amyloidosis

Objectives To identify the genotype-phenotype correlation of our patient.

Methods We describe a 13-year-old female who presented, starting at 12 years of age, recurrent episodes of high fever, pericarditis, arthralgia, arthritis of the knees, abdominal pain and marked increase in inflammatory markers (5 episodes in the first 5 months of disease). Symptoms were poorly responsive to therapy with NSAIDs and colchicine but responded to steroid therapy. Molecular analysis of the MEFV, TNFR and MVK genes did not show any pathogenic mutations. Serumamyloidlevel was normal. In the subsequent months she developed recurrent (up to daily) episodes of chest pain, skin rash and swelling of the subcutaneous tissue of limbs, trunk, joints and lips, in the absence of fever, with spontaneous resolution.

Results Molecular analysis of the CIAS1 gene revealed the presence of a c.1105C>A mutation in the heterozygous state,that predicts a L369M amino acid substitution. To the best of our knowledge this variant has never been reported. One-Hundred chromosomes were examined and the variant was not found. In order to verify the potential pathogenic effects of the L369M amino acid substitution, daily therapy with anakinra (2 mg/kg/day) was started with rapid disappearance of clinical symptoms and normalization of CRP levels in 24 hours

Conclusions The fast response to IL-1 inhibtion suggests that the disease of this patient is driven by IL-1 and support the conclusion that this novel mutation is pathogenic and may be associated with a new CAPS phenotype

  1. Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, Hoyer J, Gattorno M, Gul A, Smith J, Leslie KS, Jiménez S, Morell-Dubois S, Davis N, Patel N, Widmer A, Preiss R, Lachmann HJ. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011 Dec;70(12):2095-102. Epub 2011 Aug 21.

Disclosure of Interest None Declared

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