PMID- 10642597
OWN - NLM
STAT- MEDLINE
DCOM- 20000202
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 105
IP  - 2
DP  - 2000 Jan
TI  - Dolichol phosphate mannose synthase (DPM1) mutations define congenital disorder
      of glycosylation Ie (CDG-Ie)
PG  - 191-8
AB  - Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in
      glycoprotein biosynthesis that usually cause severe mental and psychomotor
      retardation. Different forms of CDGs can be recognized by altered isoelectric
      focusing (IEF) patterns of serum transferrin (Tf). Two patients with these
      symptoms and similar abnormal Tf IEF patterns were analyzed by metabolic labeling
      of fibroblasts with inverted question mark2-(3)Hmannose. The patients produced a 
      truncated dolichol-linked precursor oligosaccharide with 5 mannose residues,
      instead of the normal precursor with 9 mannose residues. Addition of 250 microM
      mannose to the culture medium corrected the size of the truncated
      oligosaccharide. Microsomes from fibroblasts of these patients were approximately
      95% deficient in dolichol-phosphate-mannose (Dol-P-Man) synthase activity, with
      an apparent K(m) for GDP-Man approximately 6-fold higher than normal. DPM1, the
      gene coding for the catalytic subunit of Dol-P-Man synthase, was altered in both 
      patients. One patient had a point mutation, C(274)G, causing an R(92)G change in 
      the coding sequence. The other patient also had the C(274)G mutation and a 13-bp 
      deletion that presumably resulted in an unstable transcript. Defects in DPM1
      define a new glycosylation disorder, CDG-Ie.
FAU - Kim, S
AU  - Kim S
AD  - The Burnham Institute, La Jolla, California 92037, USA.
FAU - Westphal, V
AU  - Westphal V
FAU - Srikrishna, G
AU  - Srikrishna G
FAU - Mehta, D P
AU  - Mehta DP
FAU - Peterson, S
AU  - Peterson S
FAU - Filiano, J
AU  - Filiano J
FAU - Karnes, P S
AU  - Karnes PS
FAU - Patterson, M C
AU  - Patterson MC
FAU - Freeze, H H
AU  - Freeze HH
LA  - eng
GR  - R01 DK055615/DK/NIDDK NIH HHS/United States
GR  - DK55615/DK/NIDDK NIH HHS/United States
GR  - R01 GM55695/GM/NIGMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Isoenzymes)
RN  - 0 (Transferrin)
RN  - EC 2.4.1.- (Mannosyltransferases)
RN  - EC 2.4.1.83 (dolichyl-phosphate beta-D-mannosyltransferase)
RN  - EC 3.2.1.- (Glycoside Hydrolases)
RN  - PHA4727WTP (Mannose)
SB  - AIM
SB  - IM
CIN - J Clin Invest. 2000 Jan;105(2):131-2. PMID: 10642590
MH  - Brain Diseases, Metabolic, Inborn/diagnosis/enzymology/etiology
MH  - Carbohydrate Sequence
MH  - Cells, Cultured
MH  - Congenital Disorders of
      Glycosylation/complications/diagnosis/*enzymology/*genetics
MH  - DNA Mutational Analysis
MH  - Developmental Disabilities/diagnosis
MH  - Female
MH  - Fibroblasts/cytology/enzymology
MH  - Glycoside Hydrolases/metabolism
MH  - Glycosylation
MH  - Humans
MH  - Infant
MH  - Isoelectric Focusing
MH  - Isoenzymes/deficiency/genetics/metabolism
MH  - Male
MH  - Mannose/metabolism
MH  - Mannosyltransferases/*deficiency/*genetics/metabolism
MH  - Microcephaly/diagnosis
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Seizures/diagnosis
MH  - Sequence Deletion
MH  - Transferrin/metabolism
PMC - PMC377427
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/JCI7302 [doi]
PST - ppublish
SO  - J Clin Invest. 2000 Jan;105(2):191-8. doi: 10.1172/JCI7302.