期刊
PARKINSONISM & RELATED DISORDERS
卷 21, 期 4, 页码 394-397出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2015.01.004
关键词
Parkinson's disease; Dopa responsive dystonia; GCH1; SPECK DAT imaging
资金
- Medical Research Council of the UK
- Parkinson's Disease Society of the UK
- Sandwell and West Birmingham Hospital NHS Trust
- Midland Neuroscience Teaching and Research Fund
- Stichting Parkinson Fonds, The Netherlands
Background: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. Methods: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. Results: We have identified a novel missense variant, c.5A > G, p.(G1u2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. Conclusions: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCHI genetic testing should be considered in patients with PD and a family history of DRD. (c) 2015 The Authors. Published by Elsevier Ltd.
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