PMID- 10076897
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190701
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 260
IP  - 3
DP  - 1999 Feb 5
TI  - A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive
      dystonia.
PG  - 181-4
AB  - Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the
      considerable heterogeneity of clinical phenotypic expression. To explain the
      clinical diversity, we studied a Japanese family with a novel mutant GCH
      (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio 
      than an unaffected heterozygote. Coexpression experiments using the mutant with
      wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a
      dose-dependent manner, suggesting that the dominant negative effect of a mutant
      GCH on the normal enzyme might be one of the molecular mechanisms for the
      clinical heterogeneity of DRD.
FAU - Hirano, M
AU  - Hirano M
AD  - Department of Medical Genetics, Nara Medical University, Kashihara, Japan.
FAU - Komure, O
AU  - Komure O
FAU - Ueno, S
AU  - Ueno S
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Dopamine Agents)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 63-84-3 (Dihydroxyphenylalanine)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
SB  - IM
MH  - Adult
MH  - Dihydroxyphenylalanine/*pharmacology
MH  - Dopamine Agents/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dystonia/drug therapy/*enzymology/*genetics
MH  - Female
MH  - GTP Cyclohydrolase/*genetics
MH  - Humans
MH  - Isoenzymes/genetics
MH  - Mutation, Missense/*physiology
MH  - Phenotype
MH  - Plasmids/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - S0304394098009847 [pii]
AID - 10.1016/s0304-3940(98)00984-7 [doi]
PST - ppublish
SO  - Neurosci Lett. 1999 Feb 5;260(3):181-4. doi: 10.1016/s0304-3940(98)00984-7.