Yan Ya-Ping, Zhang Bo, Mao Yan-Fang, Guo Zhang-Yu, Tian Jun, Zhao Guo-Hua, Pu Jia-Li, Luo Wei, Ouyang Zhi-Yuan, Zhang Bao-Rong
a Department of Neurology, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
b Department of Surgery, Second Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , PR China.
Int J Neurosci. 2017 Aug;127(8):694-700. doi: 10.1080/00207454.2016.1236381. Epub 2016 Oct 5.
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.
多巴反应性肌张力障碍（DRD）是一组异质性的运动障碍。关于中国DRD患者的研究报道数量有限。在本研究中，我们调查了12个中国DRD家系的临床和遗传特征。通过直接测序对GTP环化水解酶I（GCH1）、酪氨酸羟化酶（TH）和蝶呤还原酶（SPR）基因进行点突变分析。此外，对“无突变”患者进行了针对GCH1和TH的多重连接依赖探针扩增。在GCH1中检测到3个已报道的突变（IVS2-2A>G、c.293C>T、c.550C>T），而在TH中鉴定出2个复合杂合变异，其中一个是新的（c.1083C>A）。此外，在250名种族匹配的健康对照中均未检测到该新变异。DRD患者中未发现这两个基因的外显子缺失或重复突变。未发现SPR有突变。此外，一名GCH1基因存在IVS2-2A>G突变的患者表现出帕金森病体征。总之，我们在此鉴定出TH中的一个新的杂合变异（c.1083C>A）。对DRD患者进行GCH1和TH的常规筛查很重要。而对于帕金森病患者，在筛查如PARKIN、PARK7（DJ-1）和PINK1等基因后应进行GCH1突变分析。
