title: Aspartylglycosaminuria in a non-Finnish patient caused by a donor splice mutation in the glycoasparaginase gene.
abstract: Aspartylglycosaminuria is a lysosomal storage disease caused by deficient activity of glycoasparaginase (EC 3.5.1.26), and it occurs with a high frequency among Finns. We have recently shown that the molecular defect in all Finnish aspartylglycosaminuria patients examined to date consists of two single base changes in the heavy chain of glycoasparaginase (Mononen, I., Heisterkamp, N., Kaartinen, V., Williams, J. C., Yates, J. R., III, Griffin, P. R., Hood, L. E., and Groffen, J. (1991) Proc. Natl. Acad. Sci U.S.A. 88, 2941-2945). This is the first report on the identification of the molecular defect causing aspartylglycosaminuria in a patient of non-Finnish origin. Total RNA from fibroblasts of a black American aspartylglycosaminuria patient was isolated, first-strand cDNA was synthesized, and the cDNA encoding glycoasparaginase was amplified by the polymerase chain reaction. The patient's mRNA nucleotide sequence was different from the normal sequence by a deletion of 134 nucleotides at positions 807-940. Nucleotide sequence analysis of the normal glycoasparaginase gene demonstrated that the deletion corresponded precisely to a 134-base pair exon. Moreover, analysis of the splice sites demonstrated a single base change, G to T, that altered the donor splice site of the exon deleted in the patient's mRNA. This change led to an exon-skipping event resulting in a frame shift and generation of a stop codon.
authors.affiliation: Division of Medical Genetics, Children's Hospital of Los Angeles, California 90054-0700.
authors.forename: I
authors.initials: I
authors.lastname: Mononen
authors.forename: N
authors.initials: N
authors.lastname: Heisterkamp
authors.forename: V
authors.initials: V
authors.lastname: Kaartinen
authors.forename: T
authors.initials: T
authors.lastname: Mononen
authors.forename: J C
authors.initials: JC
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Groffen
mesh_terms: D000595:Amino Acid Sequence; D001227:Aspartylglucosylaminase / Q000235:genetics*; D001483:Base Sequence; D044383:Black People; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005387:Finland; D006020:Glycopeptides / Q000652:urine*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012326:RNA Splicing; D012016:Reference Values; D014481:United States / Q000208:ethnology; D001741:Black or African American
chemical_list: D006020:Glycopeptides; D009838:Oligodeoxyribonucleotides; C007872:glycoasparagines; D004247:DNA; D001227:Aspartylglucosylaminase