Mutations in the molybdenum cofactor biosynthetic genesMOCS1, MOCS2, andGEPH
- 13 May 2003
- journal article
- review article
- Published by Hindawi Limited in Human Mutation
- Vol. 21 (6), 569-576
- https://doi.org/10.1002/humu.10223
Abstract
Molybdenum cofactor deficiency in humans results in the loss of the activity of molybdoenzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. The resultant severe phenotype, which includes progressive neurological damage leading in most cases to early childhood death, results primarily from the deficiency of sulfite oxidase. All forms of molybdenum cofactor deficiency are inherited as autosomal recessive traits. The cofactor is an unstable reduced pterin with a unique four‐carbon side chain, synthesized by a complex pathway that requires the products of at least four different genes (MOCS1, MOCS2, MOCS3, and GEPH). Disease‐causing mutations have been identified in three of these genes: MOCS1, MOCS2, and GEPH. MOCS1 and MOCS2 have a bicistronic architecture; i.e., each gene encodes two proteins in different open reading frames. The protein products, MOCS1A and B and MOCS2A and B, are expressed either from different mRNAs generated by alternative splicing or by independent translation of a bicistronic mRNA. The gephyrin protein, encoded by a third locus, is required during cofactor assembly for insertion of molybdenum. A total of 32 different disease‐causing mutations, including several common to more than one family, have been identified in molybdenum cofactor‐deficient patients and their relatives. Hum Mutat 21:569–576, 2003.Keywords
This publication has 20 references indexed in Scilit:
- The bicistronic MOCS1 gene has alternative start codons on two mutually exclusive exonsMolecular Genetics and Metabolism, 2002
- Functionality of Alternative Splice Forms of the First Enzymes Involved in Human Molybdenum Cofactor BiosynthesisJournal of Biological Chemistry, 2002
- Killing the messenger: new insights into nonsense-mediated mRNA decayJCI Insight, 2002
- Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic MOCS1A and MOCS1B open reading framesRNA, 2000
- Dual Requirement for Gephyrin in Glycine Receptor Clustering and Molybdoenzyme ActivityScience, 1998
- Isolation of Two Arabidopsis cDNAs Involved in Early Steps of Molybdenum Cofactor Biosynthesis by Functional Complementation of Escherichia coli MutantsJournal of Biological Chemistry, 1995
- Biochemical investigation of a child with molybdenum cofactor deficiencyClinical Biochemistry, 1990
- Molybdenum cofactor biosynthesis in humans. Identification of two complementation groups of cofactor-deficient patients and preliminary characterization of a diffusible molybdopterin precursor.JCI Insight, 1989
- Report on a new patient with combined deficiencies of sulphite oxidase and xanthine dehydrogenase due to molybdenum cofactor deficiencyEuropean Journal of Pediatrics, 1988
- Combined deficiency of xanthine oxidase and sulphite oxidase: A defect of molybdenum metabolism or transport?Journal of Inherited Metabolic Disease, 1978