Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II

Biochem Biophys Res Commun. 2001 Apr 20;282(5):1194-200. doi: 10.1006/bbrc.2001.4719.

Abstract

Drosophila ma-l gene was suggested to encode an enzyme for sulfuration of the desulfo molybdenum cofactor for xanthine dehydrogenase (XDH) and aldehyde oxidase (AO). The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l homologue, is therefore a candidate gene responsible for classical xanthinuria type II, which involves both XDH and AO deficiencies. However, HMCS has not been identified as yet. In this study, we cloned the HMCS gene from a cDNA library prepared from liver. In two independent patients with classical xanthinuria type II, we identified a C to T base substitution at nucleotide 1255 in the HMCS gene that should cause a CGA (Arg) to TGA (Ter) nonsense substitution at codon 419. A classical xanthinuria type I patient and healthy volunteers lacked this mutation. These results indicate that a functional defect of the HMCS gene is responsible for classical xanthinuria type II, and that HMCS protein functions to provide a sulfur atom for the molybdenum cofactor of XDH and AO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aldehyde Oxidase
  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism
  • Cloning, Molecular
  • Coenzymes*
  • DNA Mutational Analysis
  • Exons
  • Humans
  • Introns
  • Japan
  • Liver / enzymology
  • Male
  • Metalloproteins / metabolism*
  • Middle Aged
  • Molecular Sequence Data
  • Molybdenum Cofactors
  • Mutation / genetics
  • Polymorphism, Genetic
  • Pteridines / metabolism*
  • Purine-Pyrimidine Metabolism, Inborn Errors / enzymology*
  • Purine-Pyrimidine Metabolism, Inborn Errors / genetics*
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Sulfurtransferases / deficiency
  • Sulfurtransferases / genetics*
  • Sulfurtransferases / metabolism
  • Xanthine Dehydrogenase / deficiency
  • Xanthine Dehydrogenase / genetics
  • Xanthine Dehydrogenase / metabolism
  • Xanthines / metabolism*

Substances

  • Coenzymes
  • Metalloproteins
  • Molybdenum Cofactors
  • Pteridines
  • RNA, Messenger
  • Xanthines
  • molybdenum cofactor
  • Xanthine Dehydrogenase
  • Aldehyde Oxidoreductases
  • Aldehyde Oxidase
  • MOCOS protein, human
  • Sulfurtransferases

Associated data

  • GENBANK/AB046692