PMID- 10401001
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - Identification and characterization of three novel missense mutations in
      mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene
      biosynthesis.
PG  - 1523-8
AB  - Mevalonic aciduria is a rare autosomal recessive metabolic disorder,
      characterized by psychomotor retardation, failure to thrive, hepatosplenomegaly, 
      anemia and recurrent febrile crises. The disorder is caused by a deficient
      activity of mevalonate kinase due to mutations in the encoding gene. Thus far,
      only two disease-causing mutations have been identified. We now report four
      different missense mutations including three novel ones, which were identified by
      sequence analysis of mevalonate kinase cDNA from three mevalonic aciduria
      patients. All mutations affect conserved amino acids. Heterologous expression of 
      the corresponding mutant mevalonate kinases as fusion proteins with glutathione S
      -transferase in Escherichia coli showed a profound effect of each of the
      mutations on enzyme activity. In addition, immunoblot analysis of fibroblast
      lysates from patients using specific antibodies against mevalonate kinase
      identified virtually no protein. These results demonstrate that the mutations
      affect not only the activity but also the stability of the mutant proteins.
FAU - Houten, S M
AU  - Houten SM
AD  - Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical
      Center, University of Amsterdam, The Netherlands.
FAU - Romeijn, G J
AU  - Romeijn GJ
FAU - Koster, J
AU  - Koster J
FAU - Gray, R G
AU  - Gray RG
FAU - Darbyshire, P
AU  - Darbyshire P
FAU - Smit, G P
AU  - Smit GP
FAU - de Klerk, J B
AU  - de Klerk JB
FAU - Duran, M
AU  - Duran M
FAU - Gibson, K M
AU  - Gibson KM
FAU - Wanders, R J
AU  - Wanders RJ
FAU - Waterham, H R
AU  - Waterham HR
LA  - eng
SI  - GENBANK/AF137598
PT  - Case Reports
PT  - Journal Article
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Butadienes)
RN  - 0 (DNA, Complementary)
RN  - 0 (Hemiterpenes)
RN  - 0 (Pentanes)
RN  - 0A62964IBU (isoprene)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.36 (mevalonate kinase)
RN  - S5UOB36OCZ (Mevalonic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Butadienes/*metabolism
MH  - Child
MH  - DNA Mutational Analysis
MH  - DNA, Complementary/*genetics
MH  - Escherichia coli/genetics
MH  - Fatal Outcome
MH  - Female
MH  - Fibroblasts/cytology/enzymology
MH  - Gene Expression Regulation, Enzymologic
MH  - *Hemiterpenes
MH  - Humans
MH  - Immunoblotting
MH  - Infant
MH  - Male
MH  - Mevalonic Acid/blood/*urine
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - *Pentanes
MH  - Phosphotransferases (Alcohol Group Acceptor)/*deficiency/genetics
MH  - Point Mutation
MH  - Sequence Homology, Amino Acid
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 - ddc172 [pii]
AID - 10.1093/hmg/8.8.1523 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1523-8. doi: 10.1093/hmg/8.8.1523.