Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome

Sander M. Houten, Janet Koster, Gerrit Jan Romeijn, Joost Frenkel, Maja Di Rocco, Ubaldo Caruso, Pierre Landrieu, Richard I. Kelley, Wietse Kuis, Bwee Tien Poll-The, K. Michael Gibson, Ronald J A Wanders, Hans R. Waterham

Research output: Contribution to journalArticle

Abstract

Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations in the encoding MVK gene. Thus far, disease-causing mutations only could be detected by analysis of MVK cDNA. We now describe the genomic organization of the human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10 introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from natural splice variants, indicating the occurrence of exon skipping. Sequence analysis of 27 HIDS and MA patients confirmed all previously reported genotypes based on cDNA analysis and identified six novel nucleotide substitutions resulting in missense or nonsense mutations, providing new insights in the genotype/phenotype relation between HIDS and MA.

Original languageEnglish
Pages (from-to)253-259
Number of pages7
JournalEuropean Journal of Human Genetics
Volume9
Issue number4
DOIs
Publication statusPublished - 2001

Keywords

  • Gene structure
  • Hyperimmunoglobulinaemia D and periodic fever syndrome
  • Inborn errors
  • Mevalonate kinase
  • Mevalonic aciduria
  • Mutations

ASJC Scopus subject areas

  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome'. Together they form a unique fingerprint.

  • Cite this

    Houten, S. M., Koster, J., Romeijn, G. J., Frenkel, J., Di Rocco, M., Caruso, U., Landrieu, P., Kelley, R. I., Kuis, W., Poll-The, B. T., Gibson, K. M., Wanders, R. J. A., & Waterham, H. R. (2001). Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. European Journal of Human Genetics, 9(4), 253-259. https://doi.org/10.1038/sj.ejhg.5200595