Human Genetics

, Volume 117, Issue 6, pp 565–570

Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase

Authors

  • Silke Leimkühler
    • Institut für Biochemie und BiologieUniversität Potsdam
  • Mathilde Charcosset
    • Hopital Debrousse
  • Philippe Latour
    • Hopital Debrousse
  • Claude Dorche
    • Hopital Debrousse
  • Soledad Kleppe
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • Fernando Scaglia
    • Department of Molecular and Human GeneticsBaylor College of Medicine
  • Irmina Szymczak
    • Institut für Humangenetik der Universität Göttingen
  • Petra Schupp
    • Institut für Humangenetik der Universität Göttingen
  • Rita Hahnewald
    • Institut für Humangenetik der Universität Göttingen
    • Institut für Humangenetik der Universität Göttingen
Original Investigation

DOI: 10.1007/s00439-005-1341-9

Cite this article as:
Leimkühler, S., Charcosset, M., Latour, P. et al. Hum Genet (2005) 117: 565. doi:10.1007/s00439-005-1341-9

Abstract

Molybdenum cofactor deficiency (MIM#252150) is a severe autosomal-recessive disorder with a devastating outcome. The cofactor is the product of a complex biosynthetic pathway involving four different genes (MOCS1, MOCS2, MOCS3 and GEPH). This disorder is caused almost exclusively by mutations in the MOCS1 or MOCS2 genes. Mutations affecting this biosynthetic pathway result in a lethal phenotype manifested by progressive neurological damage via the inactivation of the molybdenum cofactor-dependent enzyme, sulphite oxidase. Here we describe a total of ten novel disease-causing mutations in the MOCS1 and MOCS2 genes. Nine out of these ten mutations were classified as pathogenic in nature, since they create a stop codon, affect constitutive splice site positions, or change strictly conserved motifs. The tenth mutation abolishes the stop codon of the MOCS2B gene, thus elongating the corresponding protein. The mutation was expressed in vitro and was found to abolish the binding affinities of the large subunit of molybdopterin synthase (MOCS2B) for both precursor Z and the small subunit of molybdopterin synthase (MOCS2A).

Copyright information

© Springer-Verlag 2005