Two Novel Mutations in the Cystathionine β-synthase Gene of Homocystinuric Patients

Michael Y. Tsai, Paul W.K. Wong, Uttam Garg, Naomi Q. Hanson, Kerry Schwichtenberg

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: The continued identification of new mutations in the cystathionine β-synthase (CBS) gene is important in correlating the genotype/phenotype of patients with classic homocystinuria and in assessing whether heterozygosity of CBS deficiency is an important cause of mild hyperhomocysteinemia, an independent risk factor for occlusive vascular diseases. Methods and Results: Single-strand conformational polymorphism and direct nucleotide sequencing were used to detect two novel mutations in the CBS gene of three homocystinuric patients from two unrelated families. The first mutation, a G-to-A transition at nucleotide 1316 in exon 12, results in an amino acid substitution of arginine by glutamine at codon 439. The second mutation is a G-to-A transition at nucleotide 1109 in exon 10 and results in an amino acid substitution of cysteine by tyrosine at codon 370: All three patients are apparently compound heterozygotes, with one of the two novel mutations on one allele and the T833C mutation on the other allele. Conclusions: The absence of the G1316A and G1109A mutations in 216 control alleles demonstrates that these two novel mutations do not represent common polymorphisms, but rather are responsible for the defective CBS enzyme activities encoded by one of the two alleles of the CBS gene in each of the two families.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalMolecular Diagnosis
Issue number2
StatePublished - 1997
Externally publishedYes

Bibliographical note

Funding Information:
Supported in part by grants from the Van Slyke Society, the American Association of Clinical Chemistry,I nc., the Minnesota Medical Foundation of the University of Minnesota, and the American Heart Association, MinnesotaA ffiliate. Reprint requests: Michael Y. Tsai, PhD, 420 Delaware Street SE, Box 609, Mayo, Minneapolis, MN 55455-0392. 01997 Churchill Livingstone Inc.


  • Direct nucleotide sequencing
  • Genetic variants
  • Hyperhomocysteinemia
  • Single-strand conformational polymorphism

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