A novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia.
Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients. Three reported mutations (IVS2-2A>G, c.293C>T, c.550C>T) were detected in GCH1, whereas two compound heterozygous variants were identified in TH, one of which was novel (c.1083C>A). Furthermore, this novel variant was not detected in any of the 250 ethnicity-matched, healthy controls. No exon deletions or duplicate mutations in the two genes were found in patients with DRD. No mutation in SPR was found. In addition, one patient with the IVS2-2A>G mutation in GCH1 showed signs of Parkinsonism. In conclusion, we here identified a novel heterozygous variant in TH (c.1083C>A). It is important to perform routine screening of GCH1 and TH for patients with DRD. While for patients with Parkinsonism, GCH1 mutation analysis should be performed after screening of genes like PARKIN, PARK7 (DJ-1) and PINK1.
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Ya-Ping
YP
Yan
b Department of Surgery, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Bo
B
Zhang
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Yan-Fang
YF
Mao
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Zhang-Yu
ZY
Guo
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Jun
J
Tian
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Guo-Hua
GH
Zhao
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Jia-Li
JL
Pu
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Wei
W
Luo
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Zhi-Yuan
ZY
Ouyang
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Bao-Rong
BR
Zhang
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D020821:Dystonic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*; D055815:Young Adult
D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase
Chinese; GCH1 gene; Parkinsonism; SPR gene; TH gene; dopa-responsive dystonia (DRD)