PMID- 12707079
OWN - NLM
STAT- MEDLINE
DCOM- 20030507
LR  - 20220321
IS  - 0003-9942 (Print)
IS  - 0003-9942 (Linking)
VI  - 60
IP  - 4
DP  - 2003 Apr
TI  - Dopa-responsive dystonia and Tourette syndrome in a large Danish family.
PG  - 618-22
AB  - BACKGROUND: Guanosine triphosphate cyclohydrolase I (GTPCH) catalyzes the first 
      step in the synthesis of tetrahydrobiopterin (BH4). Autosomal dominantly 
      inherited defects in the GTPCH gene (GCH1) cause a form of dystonia that is 
      responsive to treatment with levodopa (dopa-responsive dystonia [DRD]). 
      OBJECTIVE: To investigate molecular and clinical aspects of DRD in a large Danish 
      family. METHODS: For analysis of the GCH1 gene, a mutation-scanning method based 
      on denaturing gradient gel electrophoresis (DGGE) was used. A novel mutation, 
      X251R, was identified in the GCH1 gene of 2 distantly related Danish patients 
      with DRD, one of whom also had Tourette syndrome (TS). Thirty-five additional 
      family members were investigated for this mutation, and 16 of them underwent 
      clinical neurological examination. RESULTS: A total of 18 patients were 
      heterozygous for the X251R allele, 16 of whom had neurological complaints 
      spanning from very mild parkinsonism to severe invalidism due to dystonia. Of 13 
      symptomatic heterozygotes who had been neurologically examined, 10 had signs of 
      dystonia or parkinsonism. Sixteen of the heterozygotes were treated with 
      levodopa, and 13 reported a treatment benefit. Three of the symptomatic 
      heterozygotes had signs of TS. CONCLUSIONS: This study confirms the large 
      variability in DRD symptoms and emphasizes the usefulness of molecular analysis 
      for diagnosis and treatment of DRD. The presence of TS is suggested to be 
      coincidental, though the development of TS-like symptoms due to mutations in GCH1 
      cannot be excluded.
FAU - Romstad, Anne
AU  - Romstad A
AD  - Department of Biochemistry, John F. Kennedy Institute, Glostrup, Denmark.
FAU - Dupont, Erik
AU  - Dupont E
FAU - Krag-Olsen, Bente
AU  - Krag-Olsen B
FAU - Ostergaard, Karen
AU  - Ostergaard K
FAU - Guldberg, Per
AU  - Guldberg P
FAU - Guttler, Flemming
AU  - Guttler F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Neurol
JT  - Archives of neurology
JID - 0372436
RN  - 0 (Dopamine Agents)
RN  - 46627O600J (Levodopa)
SB  - IM
MH  - Adult
MH  - Aged
MH  - DNA Mutational Analysis
MH  - Denmark/ethnology
MH  - Dopamine Agents/*therapeutic use
MH  - Dystonia/*diagnosis/drug therapy/ethnology/*genetics
MH  - Female
MH  - Humans
MH  - Levodopa/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - Tourette Syndrome/*diagnosis/drug therapy/ethnology/*genetics
EDAT- 2003/04/23 05:00
MHDA- 2003/05/08 05:00
CRDT- 2003/04/23 05:00
PHST- 2003/04/23 05:00 [pubmed]
PHST- 2003/05/08 05:00 [medline]
PHST- 2003/04/23 05:00 [entrez]
AID - 60/4/618 [pii]
AID - 10.1001/archneur.60.4.618 [doi]
PST - ppublish
SO  - Arch Neurol. 2003 Apr;60(4):618-22. doi: 10.1001/archneur.60.4.618.