TY - JOUR
T1 - MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever
AU - D'Osualdo, Andrea
AU - Picco, Paolo
AU - Caroli, Francesco
AU - Gattorno, Marco
AU - Giacchino, Raffaella
AU - Fortini, Patrizia
AU - Corona, Fabrizia
AU - Tommasini, Alberto
AU - Salvi, Giuseppe
AU - Specchia, Fernando
AU - Obici, Laura
AU - Meini, Antonella
AU - Ricci, Antonio
AU - Seri, Marco
AU - Ravazzolo, Roberto
AU - Martini, Alberto
AU - Ceccherini, Isabella
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - Hyper-IgD syndrome
KW - Mevalonate kinase
KW - MKD mevalonate kinase deficiency
KW - MVK common variants
KW - MVK mutation screening
KW - Periodic fever
UR - http://www.scopus.com/inward/record.url?scp=20144367084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144367084&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201323
DO - 10.1038/sj.ejhg.5201323
M3 - Article
C2 - 15536479
AN - SCOPUS:20144367084
VL - 13
SP - 314
EP - 320
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 3
ER -