A novel mutation in the CIAS1/NLRP3 gene associated with an unexpected phenotype of cryopyrin-associated periodic syndromes

Research output: Contribution to journalArticle

Abstract

Background. Cryopyrin-associated periodic syndromes (CAPS) comprise a spectrum of distinct, rare, autosomal dominant autoinflammatory disorders of increasing severity caused by NLRP3 gene mutations Methods. We describe a 13-year-old female who presented, in the initial phase of the disease, recurrent episodes of high fever, pericarditis, arthralgia, arthritis of the knees, abdominal pain and marked increase in inflammatory markers. In the subsequent months she developed recurrent episodes of chest pain, skin rash and swelling of the subcutaneous tissue, without fever, and with spontaneous resolution. Results. Molecular analysis of the CIAS1 gene revealed the presence of the Q703K variant and also a c.1105C>A mutation in the heterozygous state, that predicts a L369M amino acid substitution. The latter variant has never been reported. The L369M mutation was predicted to significantly affect protein structure (scoring as "dangerous" and "deleterious") by the Variant Effect Predictor tool. Therapy with anakinra was started with rapid disappearance of clinical symptoms and normalisation of CRP levels in 24 hours Conclusion. The rapid response to IL-1 inhibition suggests that the disease of this patient is driven by IL-1 and supports the conclusion that this novel mutation is pathogenic and may be associated with a new CAPS phenotype. The role played by the concomitant presence of the mutation Q703K remains to be clarified.

Original languageEnglish
Pages (from-to)123-125
Number of pages3
JournalClinical and Experimental Rheumatology
Volume32
Issue number1
Publication statusPublished - 2014

Keywords

  • Angioedema
  • CAPS
  • Novel
  • Pericarditis
  • Rash

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

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