A novel tyrosine hydroxylase variant in a group of Chinese patients with dopa-responsive dystonia

Abstract

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.

KEYWORDS::

• Chinese
• dopa-responsive dystonia (DRD)
• GCH1 gene
• TH gene
• SPR gene
• Parkinsonism

Acknowledgements

The authors acknowledge the patients and their families for their important help in data acquisition and the Cancer Institute of Zhejiang University for technical assistance and advice, as well as the positive DNA sample from Prof. Shang.

Declaration of Interest

The authors have no conflict of interests.

National Natural Science Foundation of China [grant number 81200984], [grant number 81271248], [grant number 81570698]; Natural Science Foundation of Zhejiang Province [grant number LY16H070003]; New Doctorate Teacher Fund from Ministry of Education [grant number 20120101120036]; National Basic Research Development Program of China [grant number 2013CB530900], [grant number 2013CB530904].

Supplementary material

Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/00207454.2016.1236381.

Additional information

Funding

National Natural Science Foundation of China [grant number 81200984], [grant number 81271248], [grant number 81570698]; Natural Science Foundation of Zhejiang Province [grant number LY16H070003]; New Doctorate Teacher Fund from Ministry of Education [grant number 20120101120036]; National Basic Research Development Program of China [grant number 2013CB530900], [grant number 2013CB530904].