Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria.

  • Kim C
  • Gallagher P
  • Guttormsen A
 et al. 
  • 12


    Mendeley users who have this article in their library.
  • 56


    Citations of this article.


Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder which results in extremely elevated levels of total plasma homocysteine (tHcy) and high risk of thromboembolic events. About half of all patients diagnosed with CBS deficiency respond to pyridoxine treatment with a significant lowering of tHcy levels. We examined 12 CBS-deficient patients from 10 Norwegian families for mutations in the CBS gene and identified mutations in 18 of the 20 CBS alleles. Five of the seven patients classified as pyridoxine-responsive contain the newly identified point mutation, G797A (R266K). This point mutation is tightly linked with a previously identified 'benign' 68 bp duplication of the intron 7-exon 8 boundary within the CBS gene. We tested the effect of all of the mutations identified on human CBS function utilizing a yeast system. Five of the six mutations had a distinguishable phenotype in yeast, indicating that they were in fact pathogenic. Interestingly, the G797A allele had no phenotype when the yeast were grown in high concentrations of pyridoxine, but a severe phenotype when grown in low concentrations, thus mirroring the behavior in humans. These studies show that the G797A mutation is an important cause of pyridoxine-responsive CBS deficiency and demonstrate the utility of yeast functional assays in the analysis of human mutations.

Author-supplied keywords

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Cloning
  • Cystathionine beta-Synthase
  • Cystathionine beta-Synthase: deficiency
  • Cystathionine beta-Synthase: genetics
  • Cystathionine beta-Synthase: physiology
  • DNA Mutational Analysis
  • Exons
  • Exons: genetics
  • Female
  • Genes
  • Genetic
  • Genotype
  • Homocystinuria
  • Homocystinuria: drug therapy
  • Homocystinuria: enzymology
  • Homocystinuria: genetics
  • Humans
  • Introns
  • Introns: genetics
  • Linkage Disequilibrium
  • Male
  • Molecular
  • Multigene Family
  • Norway
  • Point Mutation
  • Polymorphism
  • Pyridoxine
  • Pyridoxine: metabolism
  • Pyridoxine: therapeutic use
  • Recessive
  • Recombinant Fusion Proteins
  • Recombinant Fusion Proteins: metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae: drug effects
  • Saccharomyces cerevisiae: enzymology
  • Saccharomyces cerevisiae: genetics
  • Single-Stranded Conformational

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • C E Kim

  • P M Gallagher

  • a B Guttormsen

  • H Refsum

  • P M Ueland

  • L Ose

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free