Deletion of exon 8 causes glycosylasparaginase deficiency in an African American aspartylglucosaminuria (AGU) patient

FEBS Lett. 1991 Aug 19;288(1-2):173-8. doi: 10.1016/0014-5793(91)81028-7.

Abstract

We have indentified a GT-to-TT transversion at the splice donor site of intron 8 in the glycosylasparaginase gene from an African American aspartylglucosaminuria (AGU) patient. This mutation causes abnormal splicing of glycosylasparaginase pre-mRNA by joining exon 7 to 9 and excluding 134 bp exon 8. The effect of the mutation is compounded by a frame shift that occurs after the deletion site resulting in premature translational termination. The truncated AGU protein was neither catalytically active nor processed into mature alpha and beta subunits. Both this and a previously characterized Finnish AGU mutation appear to affect folding of the single-chain precursor of glycosylasparaginase and thereby prevent transport of the enzyme to lysosomes.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosamine / analogs & derivatives*
  • Acetylglucosamine / urine
  • African Continental Ancestry Group / genetics
  • Amino Acid Sequence
  • Aspartylglucosaminuria*
  • Aspartylglucosylaminase / genetics
  • Aspartylglucosylaminase / metabolism
  • Base Sequence
  • Child
  • Chromosome Deletion*
  • Exons / genetics
  • Fluorescent Antibody Technique
  • Glycosuria / enzymology
  • Glycosuria / genetics*
  • Glycosuria / physiopathology
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics
  • Polymerase Chain Reaction
  • Protein Conformation
  • RNA Splicing / genetics

Substances

  • N-acetylglucosaminylasparagine
  • Aspartylglucosylaminase
  • Acetylglucosamine

Associated data

  • GENBANK/S53371
  • GENBANK/S53390
  • GENBANK/X58797
  • GENBANK/X58798
  • GENBANK/X58799
  • GENBANK/X58800
  • GENBANK/X58801
  • GENBANK/X58802
  • GENBANK/X58803
  • GENBANK/X61958