Two novel missense mutations in the cystathionine β-synthase gene in homocystinuric patients

  title={Two novel missense mutations in the cystathionine $\beta$-synthase gene in homocystinuric patients},
  author={Leo A. J. Kluijtmans and Henk J Blom and Godfried H. J. Boers and Bernard A. van Oost and Frans J. M. Trijbels and Lambert P. Heuvel},
  journal={Human Genetics},
Direct sequencing of the coding region of the cystathionine β-synthase (CBS) gene in two homocystinuric patients revealed the presence of two novel missense mutations. The first mutation, a 1111G → A transition, resulted in the substitution of the evolutionary conserved valine-371 by a methionine residue (V371M) and created a new NlaIII restriction site. The second mutation, a G→A transition at base-pair 494, resulted in an amino acid change from cysteine to tyrosine (C165Y) and abolished a… 
8 Citations
Four novel mutations at the cystathionine β-synthase locus causing homocystinuria
We describe four new mutations in the cystathionine β-synthase gene: three point mutations localized in exons 3, 9 and 10 and one mutation in exon 12 which results in stop codon. Homocystinuria due
Hyperhomocysteinemia and dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9
A CBS G307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G 307S mutation in the CBS gene is a causative factor for dyslipids.
Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles
Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment.
Etoposide phosphate, the water soluble prodrug of etoposide
An elevated plasma homocysteine level may result from various enviromental and genetic factors. Hereditary causes of severe hyperhomo-cysteinaemia are very rare and usually lead to disease in
Methods in assessing homocysteine metabolism.
In the current review emphasis will be on the estimation of homocysteine, and evaluation of one of the common mutations encountered in the metabolism of this amino acid.
Homocysteine in coronary artery disease
In this thesis we review epidemiological evidence of the relationship between homocysteine and cardiovascular disease with an introduction to homocysteine metabolism in relation to the genetics of


Molecular basis of phenotype expression in homocystinuria
  • J. Kraus
  • Biology
    Journal of Inherited Metabolic Disease
  • 2004
Screening for mutations by expressing patient cDNA segments in E. coli permitted us to separate the parental CBS alleles, localize each mutation within one third of the cDNA, and functionally analyse the mutant protein.
Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria.
The G307S mutation was detected in 50% (9 of 18) of the Celtic alleles in the authors' series, which suggests that Celtic (Irish/English/Scottish/French) ancestry in either one or both parents is probably associated with pyridoxine responsiveness.
Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells.
The human CBS cDNA sequence of 2,554 nucleotides encoding the CBS subunit of 551 amino acids is reported and it is demonstrated that expression of the human enzyme in CHO cells yields enzymatically active protein of the expected size with a half-life of approximately 14 hrs.
The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17.
The human gene for cystathionine beta-synthase (CBS) and the gene for alpha A-crystalline (CRYA1/Crya-1 or Acry-1) form a conserved linkage group on human (HSA) chromosome region 21q22.3 and mouse (MMU) chromosome 17 region A-C.
Methionine metabolism in mammals. Distribution of homocysteine between competing pathways.
Using an in vitro system which contained enzymes, substrates, and other reactants at concentrations which approximated the in vivo conditions in rat liver, it was demonstrated that the adaptation from a high protein diet to a low protein diet is achieved by a significant increase in betaine homocysteine methyltransferase, and 83% reduction in cystathionine synthase, which contributes significantly to the regulation of the pathway.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in
(eds) The metabolic basis of inherited disease, 6th edn
  • 1989
Disorders of transsulfuration
Disorders of transsulfura­ tion
  • The metabolic basis of inherited disease,
  • 1989
The gene for cystathionine ß-synthase (CBS) maps to the subtelomeric re­ gion on human chromosome 21q and to proximal mouse chro­ mosome 17
  • Am J Hum Genet
  • 1988