In vitro mutagenesis helps to unravel the biological consequences of aspartylglucosaminuria mutation

Genomics. 1991 Sep;11(1):206-11. doi: 10.1016/0888-7543(91)90120-4.


Aspartylglucosaminuria (AGU) is a lysosomal storage disease resulting in severe mental retardation. We have recently reported that mutations in the aspartylglucosaminidase (AGA) locus are responsible for this disease. About 90% of reported AGU cases are found in Finland, and we have shown that the vast majority (98%) of AGU alleles in this isolated population contain two point mutations located 5 bp apart. We expressed these Arg161----Gln and Cys163----Ser mutations separately in vitro and demonstrated that deficient enzyme activity is caused by the Cys163----Ser mutation, whereas the Arg161----Gln substitution represents a rare polymorphism. Further analyses of in vitro expressed AGA proteins and the enzyme purified from an AGU patient revealed that Cys163 participates in and S-S bridge. The absence of this covalent cross-link in the mutated protein most probably results in disturbed folding of the polypeptide chain and a consequent decrease in its intracellular stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartylglucosylaminase / chemistry
  • Aspartylglucosylaminase / genetics*
  • Aspartylglucosylaminase / metabolism
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Cysteine / chemistry
  • DNA
  • DNA Mutational Analysis
  • Disulfides / chemistry
  • Humans
  • Lysosomal Storage Diseases / enzymology
  • Lysosomal Storage Diseases / genetics*
  • Lysosomal Storage Diseases / urine
  • Molecular Sequence Data
  • Mutagenesis


  • Disulfides
  • DNA
  • Aspartylglucosylaminase
  • Cysteine