Journal of Inherited Metabolic Disease

, Volume 17, Issue 4, pp 383–390 | Cite as

Molecular basis of phenotype expression in homocystinuria

  • J. P. Kraus
Komrower Lecture

Summary

Cystathionine β-synthase (CBS) deficiency is the most common cause of homocystinuria in humans. The human gene maps to chromosome 21q22.3 and encodes the CBS subunit of 551 amino acid residues (63 kDa). CBS, a tetramer of these subunits, binds its two substrates, homocysteine and serine, and three additional ligands: pyridoxal 5′-phosphate,S-adenosylmethionine, and haem. Screening for mutations by expressing patient cDNA segments inE. coli permitted us to separate the parental CBS alleles, localize each mutation within one third of the cDNA, and functionally analyse the mutant protein. Using this method we identified the first 14 mutations in homocystinuria. The most common mutation in patients of predominantly ‘Celtic’ origin is the G919A transition which substitutes serine for glycine 307.

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Copyright information

© Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers 1994

Authors and Affiliations

  • J. P. Kraus
    • 1
  1. 1.Departments of Pediatrics and Cellular/Structural Biology, C-233University of Colorado School of MedicineDenverUSA

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