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

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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 .