PMID- 10642602
OWN - NLM
STAT- MEDLINE
DCOM- 20000202
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 105
IP  - 2
DP  - 2000 Jan
TI  - Deficiency of dolichol-phosphate-mannose synthase-1 causes congenital disorder of
      glycosylation type Ie.
PG  - 233-9
AB  - Congenital disorders of glycosylation (CDG), formerly known as
      carbohydrate-deficient glycoprotein syndromes, lead to diseases with variable
      clinical pictures. We report the delineation of a novel type of CDG identified in
      2 children presenting with severe developmental delay, seizures, and dysmorphic
      features. We detected hypoglycosylation on serum transferrin and cerebrospinal
      fluid beta-trace protein. Lipid-linked oligosaccharides in the endoplasmic
      reticulum of patient fibroblasts showed an accumulation of the dolichyl
      pyrophosphate Man(5)GlcNAc(2) structure, compatible with the reduced
      dolichol-phosphate-mannose synthase (DolP-Man synthase) activity detected in
      these patients. Accordingly, 2 mutant alleles of the DolP-Man synthase DPM1 gene,
      1 with a 274C>G transversion, the other with a 628delC deletion, were detected in
      both siblings. Complementation analysis using DPM1-null murine Thy1-deficient
      cells confirmed the detrimental effect of both mutations on the enzymatic
      activity. Furthermore, mannose supplementation failed to improve the
      glycosylation status of DPM1-deficient fibroblast cells, thus precluding a
      possible therapeutic application of mannose in the patients. Because DPM1
      deficiency, like other subtypes of CDG-I, impairs the assembly of N-glycans, this
      novel glycosylation defect was named CDG-Ie.
FAU - Imbach, T
AU  - Imbach T
AD  - Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland.
FAU - Schenk, B
AU  - Schenk B
FAU - Schollen, E
AU  - Schollen E
FAU - Burda, P
AU  - Burda P
FAU - Stutz, A
AU  - Stutz A
FAU - Grunewald, S
AU  - Grunewald S
FAU - Bailie, N M
AU  - Bailie NM
FAU - King, M D
AU  - King MD
FAU - Jaeken, J
AU  - Jaeken J
FAU - Matthijs, G
AU  - Matthijs G
FAU - Berger, E G
AU  - Berger EG
FAU - Aebi, M
AU  - Aebi M
FAU - Hennet, T
AU  - Hennet T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CD59 Antigens)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Lipocalins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oligosaccharides)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Thy-1 Antigens)
RN  - 0 (Transferrin)
RN  - EC 2.4.1.- (ALG3 protein, S cerevisiae)
RN  - EC 2.4.1.- (DPM2 protein, human)
RN  - EC 2.4.1.- (Mannosyltransferases)
RN  - EC 2.4.1.83 (dolichyl-phosphate beta-D-mannosyltransferase)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.2 (prostaglandin R2 D-isomerase)
RN  - PHA4727WTP (Mannose)
SB  - AIM
SB  - IM
CIN - J Clin Invest. 2000 Jan;105(2):131-2. PMID: 10642590
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - CD59 Antigens/metabolism
MH  - Carbohydrate Sequence
MH  - Carrier Proteins/genetics
MH  - Cells, Cultured
MH  - Child, Preschool
MH  - Congenital Disorders of
      Glycosylation/complications/*enzymology/*genetics/pathology
MH  - Endoplasmic Reticulum/metabolism
MH  - Female
MH  - Fibroblasts/cytology/drug effects/enzymology
MH  - Fungal Proteins/genetics
MH  - Glycosylation
MH  - Humans
MH  - Infant
MH  - Intramolecular Oxidoreductases/cerebrospinal fluid
MH  - Isoenzymes/deficiency/genetics/metabolism
MH  - Lipocalins
MH  - Male
MH  - Mannose/metabolism/pharmacology
MH  - Mannosyltransferases/*deficiency/*genetics/metabolism
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oligosaccharides/metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Thy-1 Antigens/biosynthesis
MH  - Transferrin/metabolism
PMC - PMC377434
EDAT- 2000/01/22 00:00
MHDA- 2000/01/22 00:01
CRDT- 2000/01/22 00:00
PHST- 2000/01/22 00:00 [pubmed]
PHST- 2000/01/22 00:01 [medline]
PHST- 2000/01/22 00:00 [entrez]
AID - 10.1172/JCI8691 [doi]
PST - ppublish
SO  - J Clin Invest. 2000 Jan;105(2):233-9. doi: 10.1172/JCI8691.