title: MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever.
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.
authors.affiliation: Divisione Pediatria II Clinica Pediatrica, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Osualdo
authors.forename: Paolo
authors.initials: P
authors.lastname: Picco
authors.forename: Francesco
authors.initials: F
authors.lastname: Caroli
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giacchino
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fortini
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Corona
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Salvi
authors.forename: Fernando
authors.initials: F
authors.lastname: Specchia
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Antonella
authors.initials: A
authors.lastname: Meini
authors.forename: Antonio
authors.initials: A
authors.lastname: Ricci
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
mesh_terms: D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications / Q000235:genetics; D007072:Immunoglobulin D / Q000097:blood; D007223:Infant; D007558:Italy; D008297:Male; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics*
chemical_list: D007072:Immunoglobulin D; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase