A novel missense mutation of the GTP cyclohydrolase I gene in a Korean family with hereditary progressive dystonia/dopa-responsive dystonia.
Hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD) shows the considerable heterogeneity of clinical phenotypic expression and a dramatic sustained response to levodopa. The autosomal dominant HPD/DRD is caused by mutations in the gene coding GTP cyclohydrolase I (GCH I), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. Previous studies suggested that normal [18F]Dopa positron emission tomography or [123I]beta-CIT single-photon emission computed tomography (SPECT) imaging, indicating intact structural integrity of nigrostriatal neurons, may be useful for differentiating HPD/DRD from clinically similar conditions such as juvenile Parkinson's disease with dystonia that have a considerably poorer prognosis. We here report a Korean family affected with HPD/DRD due to a novel missense mutation of the GCH I gene (T-->G mutation in exon 2), Met 137 Arg, which may change the conformation of the binding site of GCH I. The clinical features are considerably variable within the family. We documented normal striatal uptake of [123I]IPT, a dopamine transporter ligand with fast washout kinetics, in our patients by using SPECT. This method can be helpful in diagnosing HPD/DRD in uncertain cases.
Kang
Ji-Hoon
JH
Department of Neurology, College of Medicine, Cheju National University, Cheju, South Korea.
Kang
Sa-Yoon
SY
Kang
Hee-Kyoung
HK
Koh
Young-Sang
YS
Im
Joo-Hyuk
JH
Lee
Myoung Chong
MC
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004295:Dihydroxyphenylalanine / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000627:therapeutic use*; D020821:Dystonic Disorders / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D010375:Pedigree; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
D015259:Dopamine Agents; D019275:Radiopharmaceuticals; D014326:Tropanes; C087210:N-(3-iodopropen-1-yl)-2-carbomethoxy-3-(4-chlorophenyl)tropane; D004295:Dihydroxyphenylalanine; D006136:GTP Cyclohydrolase