PMID- 10359825
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 12
DP  - 1999 Jun 8
TI  - A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes
      carbohydrate-deficient glycoprotein syndrome type-Ic.
PG  - 6982-7
AB  - Carbohydrate-deficient glycoprotein syndrome (CDGS) represents a class of genetic
      diseases characterized by abnormal N-linked glycosylation. CDGS patients show a
      large number of glycoprotein abnormalities resulting in dysmorphy,
      encephalopathy, and other organ disorders. The majority of CDGSs described to
      date are related to an impaired biosynthesis of dolichyl pyrophosphate-linked
      Glc3Man9GlcNAc2 in the endoplasmic reticulum. Recently, we identified in four
      related patients a novel type of CDGS characterized by an accumulation of
      dolichyl pyrophosphate-linked Man9GlcNAc2. Elaborating on the analogy of this
      finding with the phenotype of alg5 and alg6 Saccharomyces cerevisiae strains, we 
      have cloned and analyzed the human orthologs to the ALG5 dolichyl phosphate
      glucosyltransferase and ALG6 dolichyl pyrophosphate Man9GlcNAc2
      alpha1,3-glucosyltransferase in four novel CDGS patients. Although ALG5 was not
      altered in the patients, a C-->T transition was detected in ALG6 cDNA of all four
      CDGS patients. The mutation cosegregated with the disease in a Mendelian
      recessive manner. Expression of the human ALG5 and ALG6 cDNA could partially
      complement the respective S. cerevisiae alg5 and alg6 deficiency. By contrast,
      the mutant ALG6 cDNA of CDGS patients failed to revert the hypoglycosylation
      observed in alg6 yeasts, thereby proving a functional relationship between the
      alanine to valine substitution introduced by the C-->T transition and the CDGS
      phenotype. The mutation in the ALG6 alpha1,3-glucosyltransferase gene defines an 
      additional type of CDGS, which we propose to refer to as CDGS type-Ic.
FAU - Imbach, T
AU  - Imbach T
AD  - Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057
      Zurich, Switzerland.
FAU - Burda, P
AU  - Burda P
FAU - Kuhnert, P
AU  - Kuhnert P
FAU - Wevers, R A
AU  - Wevers RA
FAU - Aebi, M
AU  - Aebi M
FAU - Berger, E G
AU  - Berger EG
FAU - Hennet, T
AU  - Hennet T
LA  - eng
SI  - GENBANK/AF102850
SI  - GENBANK/AF102851
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA, Complementary)
RN  - 0 (Membrane Proteins)
RN  - EC 2.4.1.- (ALG6 protein, human)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 2.4.1.- (dolichyl pyrophosphate Man(9)GlcNAc(2) alpha1,3-glucosyltransferase)
RN  - EC 2.4.1.117 (ALG5 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Congenital Disorders of Glycosylation/*genetics
MH  - DNA, Complementary/analysis/genetics
MH  - Glucosyltransferases/*genetics
MH  - Humans
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Saccharomyces cerevisiae/genetics
MH  - Sequence Alignment
MH  - Sequence Analysis
PMC - PMC22030
EDAT- 1999/06/09 00:00
MHDA- 1999/06/09 00:01
CRDT- 1999/06/09 00:00
PHST- 1999/06/09 00:00 [pubmed]
PHST- 1999/06/09 00:01 [medline]
PHST- 1999/06/09 00:00 [entrez]
AID - 10.1073/pnas.96.12.6982 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6982-7. doi: 10.1073/pnas.96.12.6982.