Candidate gene studies in focal dystonia.
BACKGROUND
Genetic susceptibility factors for focal idiopathic torsion dystonia (F-ITD) are not established. Mutations in the DYT1 gene can cause focal dystonia, and an association with a polymorphism in the D5 receptor gene (DRD5) has been reported but not confirmed.


OBJECTIVE
To investigate a possible role of DYT1 polymorphisms, a CA repeat in the D5 receptor gene (DRD5), the human leukocyte antigen (HLA)-DRB locus, and four polymorphisms in the homocysteine metabolism in the pathogenesis of F-ITD.


METHODS
Initially, 100 German patients and 100 matched control subjects were investigated. A second French population with 121 F-ITD patients and matched control subjects was also studied.


RESULTS
Two polymorphisms of the beta-cystathionine synthase gene were associated with F-ITD in the German population, but this finding was not replicated in a second independent F-ITD patient and control group of French origin. None of the other investigated polymorphisms was associated with F-ITD. The authors failed to confirm a previously reported association with a polymorphism in DRD5.


CONCLUSIONS
No evidence for an involvement of DYT1, DRD5, HLA-DRB, or polymorphisms in the homocysteine pathway in the pathogenesis of F-ITD was found.
Department of Neurology, Philipps University, Marburg, Germany.
D
D
Sibbing
F
F
Asmus
I R
IR
König
S
S
Tezenas du Montcel
M
M
Vidailhet
S
S
Sangla
W H
WH
Oertel
A
A
Brice
A
A
Ziegler
T
T
Gasser
O
O
Bandmann
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D003541:Cystathionine beta-Synthase / Q000235:genetics; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050641:Receptors, Dopamine D5
C493605:DRD5 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018832:Molecular Chaperones; D017447:Receptors, Dopamine D1; C108175:TOR1A protein, human; D050641:Receptors, Dopamine D5; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase