PMID- 10369261
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 2
DP  - 1999 Jun
TI  - Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D
      and periodic fever syndrome.
PG  - 175-7
AB  - Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is an
      autosomal recessive disorder characterized by recurrent episodes of fever
      associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin
      rash. Diagnostic hallmark of HIDS is a constitutively elevated level of serum
      immunoglobulin D (IgD), although patients have been reported with normal IgD
      levels. To determine the underlying defect in HIDS, we analysed urine of several 
      patients and discovered increased concentrations of mevalonic acid during severe 
      episodes of fever, but not between crises. Subsequent analysis of cells from four
      unrelated HIDS patients revealed reduced activities of mevalonate kinase (MK;
      encoded by the gene MVK), a key enzyme of isoprenoid biosynthesis. Sequence
      analysis of MVK cDNA from the patients identified three different mutations, one 
      of which was common to all patients. Expression of the mutant cDNAs in
      Escherichia coli showed that all three mutations affect the activity of the
      encoded proteins. Moreover, immunoblot analysis demonstrated a deficiency of MK
      protein in patient fibroblasts, indicating a protein-destabilizing effect of the 
      mutations.
FAU - Houten, S M
AU  - Houten SM
AD  - Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical
      Center, University of Amsterdam, The Netherlands.
FAU - Kuis, W
AU  - Kuis W
FAU - Duran, M
AU  - Duran M
FAU - de Koning, T J
AU  - de Koning TJ
FAU - van Royen-Kerkhof, A
AU  - van Royen-Kerkhof A
FAU - Romeijn, G J
AU  - Romeijn GJ
FAU - Frenkel, J
AU  - Frenkel J
FAU - Dorland, L
AU  - Dorland L
FAU - de Barse, M M
AU  - de Barse MM
FAU - Huijbers, W A
AU  - Huijbers WA
FAU - Rijkers, G T
AU  - Rijkers GT
FAU - Waterham, H R
AU  - Waterham HR
FAU - Wanders, R J
AU  - Wanders RJ
FAU - Poll-The, B T
AU  - Poll-The BT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Immunoglobulin D)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.36 (mevalonate kinase)
RN  - S5UOB36OCZ (Mevalonic Acid)
SB  - IM
CIN - Nat Genet. 1999 Jun;22(2):121-2. PMID: 10369246
MH  - Amino Acid Substitution
MH  - Cloning, Molecular
MH  - Escherichia coli
MH  - Female
MH  - Fever/enzymology/*genetics
MH  - Genes, Recessive
MH  - Humans
MH  - Hypergammaglobulinemia/enzymology/*genetics
MH  - *Immunoglobulin D
MH  - Indonesia
MH  - Lymphocytes/enzymology
MH  - Male
MH  - Mevalonic Acid/blood
MH  - Netherlands
MH  - Periodicity
MH  - Phosphotransferases (Alcohol Group Acceptor)/biosynthesis/*genetics
MH  - *Point Mutation
MH  - Recombinant Proteins/biosynthesis
MH  - Recurrence
MH  - Syndrome
EDAT- 1999/06/16 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/16 10:00
PHST- 1999/06/16 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/16 10:00 [entrez]
AID - 10.1038/9691 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jun;22(2):175-7. doi: 10.1038/9691.