Deletion of exon 8 causes glycosylasparaginase deficiency in an African American aspartylglucosaminuria (AGU) patient.
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.
Fisher
K J
KJ
Department of Molecular and Cell Biology, Althouse Lab, Pennsylvania State University, University Park 16802.
Aronson
N N
NN
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000652:urine; D000595:Amino Acid Sequence; D054880:Aspartylglucosaminuria; D001227:Aspartylglucosylaminase / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D005091:Exons / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006029:Glycosuria / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012326:RNA Splicing / Q000235:genetics; D001741:Black or African American
C000009:N-acetylglucosaminylasparagine; D001227:Aspartylglucosylaminase; D000117:Acetylglucosamine