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Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome

Houten, Sander M. ; Kuis, Wietse ; Duran, Marinus ; De Koning, Tom J. LU ; Van Royen-Kerkhof, Annet ; Romeijn, Gerrit J. ; Frenkel, Joost ; Dorland, Lambertus ; De Barse, Martina M.J. and Huijbers, Wim A.R. , et al. (1999) In Nature Genetics 22(2). p.175-177
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
22
issue
2
pages
3 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:0032987982
  • pmid:10369261
ISSN
1061-4036
DOI
10.1038/9691
language
English
LU publication?
no
id
215703e9-73a3-445d-af6c-8e58880f3a9a
date added to LUP
2020-03-03 19:17:38
date last changed
2024-06-27 15:13:25
@article{215703e9-73a3-445d-af6c-8e58880f3a9a,
  abstract     = {{<p>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.</p>}},
  author       = {{Houten, Sander M. and Kuis, Wietse and Duran, Marinus and De Koning, Tom J. and Van Royen-Kerkhof, Annet and Romeijn, Gerrit J. and Frenkel, Joost and Dorland, Lambertus and De Barse, Martina M.J. and Huijbers, Wim A.R. and Rijkers, Ger T. and Waterham, Hans R. and Wanders, Ronald J.A. and Poll-The, Bwee Tien}},
  issn         = {{1061-4036}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{175--177}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome}},
  url          = {{http://dx.doi.org/10.1038/9691}},
  doi          = {{10.1038/9691}},
  volume       = {{22}},
  year         = {{1999}},
}