A novel missense mutation of the GTP cyclohydrolase 1 gene in a Taiwanese family with dopa-responsive dystonia: A case report

作者：Yang Chen Chih; Wang Wei Chung; Yeh Tu Hsueh; Chen Tzu Hsuan; Liu Yen Liang; Lu Ming Kuei; Lu Chin Song; Tsai Chon Haw^*

来源：Clinical Neurology and Neurosurgery, 2018, 165: 21-23.

DOI：10.1016/j.clineuro.2017.12.018

• Dopa-responsive dystonia
• Autosomal-dominant GCH1 deficiency
• Diurnal fluctuation
• Missense mutation
• DYT5a

Background: Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by early onset dystonia and a dramatic response to relatively low doses of levodopa. The autosomal dominant DRD is caused by mutations in the gene coding GTP cyclohydrolase 1 (GCH1), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. We herein report a novel gene mutation causally links to DRD.
Subject and Methods: A 23-year-old woman, presented with a history of gait abnormality and leg dystonia at age 15. Her symptoms were worsened especially in recent 2 years prior to visiting neurological clinic. In view of typical diurnal variation of dystonia, a therapeutic trial with levodopa was given and there was a dramatic response. Hence, a diagnosis of DRD was tentatively made. In addition, her father has leg dystonia since his 14 years old with leg tremor. Her 2 uncles and probably her 2 grandaunts also have limbs tremor. Genetic analysis by using PCR-direct sequencing revealed a novel point mutation (c.263G > T:p.Arg88Leu) in GCH1, including her father and asymptomatic eldest sister.
Conclusion: We here report a Taiwanese family afflicted with DRD due to a novel missense mutation of the GCH1. The clinical features are considerably variable within the family. The findings extend the genotypic and clinical spectrum of DRD.

• 出版日期2018-2
• 单位中国医科大学