MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever

Andrea D'Osualdo, Paolo Picco, Francesco Caroli, Marco Gattorno, Raffaella Giacchino, Patrizia Fortini, Fabrizia Corona, Alberto Tommasini, Giuseppe Salvi, Fernando Specchia, Laura Obici, Antonella Meini, Antonio Ricci, Marco Seri, Roberto Ravazzolo, Alberto Martini, Isabella Ceccherini

Research output: Contribution to journalArticle

Abstract

Autosomal recessive autoinflammatory disorder caused by mutations of the mevalonate kinase gene (MVK), leading to mild, incomplete MK enzyme deficiency (MKD), has been known so far as Hyper-IgD and periodic fever syndrome (HIDS) and regarded as mostly occurring in Northern Europe. Here we report the results of the molecular characterization of the first Italian series of patients affected with autoinflammatory disorders and periodic fever. A total of 13 different mutations, scattered throughout the MVK coding region, were identified in either homozygous or compound heterozygous state in 15 patients. The mutation leading to the V377I amino-acid change, already described also in other series, resulted the most common with a frequency of 50% of all MKD alleles. Among the other mutations, eight had never been described before, including an interstitial deletion of 19 nucleotides in exon 2. In addition to these nucleotide changes, private and polymorphic MVK variants have been detected in the patients under analysis and checked also in a set of control individuals. Clinical features are reported for each of the 15 MKD patients, and life-threatening infections and systemic amyloidosis presented as unexpected MKD-related complications. Our study demonstrates that MKD is a common cause of recurrent fever also in the Italian population, where it is associated with both a wide spectrum of previously unreported MVK mutations and peculiar phenotypic features.

Original languageEnglish
Pages (from-to)314-320
Number of pages7
JournalEuropean Journal of Human Genetics
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2005

Keywords

  • Hyper-IgD syndrome
  • Mevalonate kinase
  • MKD mevalonate kinase deficiency
  • MVK common variants
  • MVK mutation screening
  • Periodic fever

ASJC Scopus subject areas

  • Genetics(clinical)

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