title: Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId.
abstract: Deficiency of the Golgi enzyme UDP-Gal:N-acetylglucosamine beta-1,4-galactosyltransferase I (beta4GalT I) (E.C.2.4.1.38) causes a new congenital disorder of glycosylation (CDG), designated type IId (CDG-IId), a severe neurologic disease characterized by a hydrocephalus, myopathy, and blood-clotting defects. Analysis of oligosaccharides from serum transferrin by HPLC, mass spectrometry, and lectin binding revealed the loss of sialic acid and galactose residues. In skin fibroblasts and leukocytes, galactosyltransferase activity was reduced to 5% that of controls. In fibroblasts, a truncated polypeptide was detected that was about 12 kDa smaller in size than wild-type beta4GalT I and that failed to localize to the Golgi apparatus. Sequencing of the beta4GalT I cDNA and gene revealed an insertion of a single nucleotide (1031-1032insC) leading to premature translation stop and loss of the C-terminal 50 amino acids of the enzyme. The patient was homozygous and his parents heterozygous for this mutation. Expression of a corresponding mutant cDNA in COS-7 cells led to the synthesis of a truncated, inactive polypeptide, which localized to the endoplasmic reticulum.
authors.affiliation: Abteilung Biochemie II, Georg-August-Universität Göttingen, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany.
authors.forename: Bengt
authors.initials: B
authors.lastname: Hansske
authors.forename: Christian
authors.initials: C
authors.lastname: Thiel
authors.forename: Torben
authors.initials: T
authors.lastname: Lübke
authors.forename: Martin
authors.initials: M
authors.lastname: Hasilik
authors.forename: Stefan
authors.initials: S
authors.lastname: Höning
authors.forename: Verena
authors.initials: V
authors.lastname: Peters
authors.forename: Peter H
authors.initials: PH
authors.lastname: Heidemann
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: Eric G
authors.initials: EG
authors.lastname: Berger
authors.forename: Kurt
authors.initials: K
authors.lastname: von Figura
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
mesh_terms: D002478:Cells, Cultured; D002675:Child, Preschool; D002846:Chromatography, Affinity; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005690:Galactose / Q000378:metabolism; D006023:Glycoproteins / Q000097:blood*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D021381:Protein Transport / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014168:Transferrin / Q000032:analysis*; D014531:Uridine Diphosphate Galactose / Q000172:deficiency* / Q000378:metabolism; D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D014168:Transferrin; D014531:Uridine Diphosphate Galactose; D006022:beta-N-Acetylglucosaminylglycopeptide beta-1,4-Galactosyltransferase; D005690:Galactose