PMID- 10400999
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional
      protein deficiency.
PG  - 1509-16
AB  - D-bifunctional protein is involved in the peroxisomal beta-oxidation of very long
      chain fatty acids, branched chain fatty acids and bile acid intermediates. In
      line with the central role of D-bifunctional protein in the beta-oxidation of
      these three types of fatty acids, all patients with D-bifunctional protein
      deficiency so far reported in the literature show elevated levels of very long
      chain fatty acids, branched chain fatty acids and bile acid inter-mediates. In
      contrast, we now report two novel patients with D-bifunctional protein deficiency
      who both have normal levels of bile acid intermediates. Complementation analysis 
      and D-bifunctional protein activity measurements revealed that both patients had 
      an isolated defect in the enoyl-CoA hydratase domain of D-bifunctional protein.
      Subsequent mutation analysis showed that both patients are homozygous for a
      missense mutation (N457Y), which is located in the enoyl-CoA hydratase coding
      part of the D-bifunctional protein gene. Expression of the mutant protein in the 
      yeast Saccharomyces cerevisiae confirmed that the N457Y mutation is the
      disease-causing mutation. Immunoblot analysis of patient fibroblast homogenates
      showed that the protein levels of full-length D-bifunctional protein were
      strongly reduced while the enoyl-CoA hydratase component produced after
      processing within the peroxisome was undetectable, which indicates that the
      mutation leads to an unstable protein.
FAU - van Grunsven, E G
AU  - van Grunsven EG
AD  - Department of Pediatrics, University of Amsterdam, Academic Medical Center, The
      Netherlands.
FAU - Mooijer, P A
AU  - Mooijer PA
FAU - Aubourg, P
AU  - Aubourg P
FAU - Wanders, R J
AU  - Wanders RJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Multienzyme Complexes)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.- (3-Hydroxyacyl CoA Dehydrogenases)
RN  - EC 4.2.1.- (Hydro-Lyases)
RN  - EC 4.2.1.107 (Peroxisomal Multifunctional Protein-2)
RN  - EC 4.2.1.119 (HSD17B4 protein, human)
RN  - EC 4.2.1.17 (Enoyl-CoA Hydratase)
SB  - IM
MH  - *17-Hydroxysteroid Dehydrogenases
MH  - 3-Hydroxyacyl CoA Dehydrogenases/deficiency/genetics
MH  - Amino Acid Substitution
MH  - Cells, Cultured
MH  - DNA Mutational Analysis
MH  - Enoyl-CoA Hydratase/*deficiency/genetics
MH  - Fatal Outcome
MH  - Genetic Complementation Test
MH  - Humans
MH  - Hydro-Lyases/deficiency/genetics
MH  - Infant
MH  - Male
MH  - Multienzyme Complexes/deficiency/genetics
MH  - Peroxisomal Disorders/enzymology/genetics/pathology
MH  - Peroxisomal Multifunctional Protein-2
MH  - Point Mutation
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - ddc163 [pii]
AID - 10.1093/hmg/8.8.1509 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1509-16. doi: 10.1093/hmg/8.8.1509.