オオヤマ　ゲンコウ   OYAMA Genko   大山　彦光    所属   埼玉医科大学  医学部 脳神経内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.
掲載誌名	正式名：Journal of neurology
掲載区分	国外
巻・号・頁	265(8),1860-1870頁
著者・共著者	Hiroyo Yoshino,Kenya Nishioka,Yuanzhe Li,Yutaka Oji,Genko Oyama,Taku Hatano,Yutaka Machida,Yasushi Shimo,Arisa Hayashida,Aya Ikeda,Kaoru Mogushi,Yasuro Shibagaki,Ai Hosaka,Hiroshi Iwanaga,Junko Fujitake,Takekazu Ohi,Daigo Miyazaki,Yoshiki Sekijima,Mitsuaki Oki,Hirofumi Kusaka,Ken-Ichi Fujimoto,Yoshikazu Ugawa,Manabu Funayama,Nobutaka Hattori
発行年月	2018/08
概要	Guanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with increased risk for dopa-responsive dystonia (DRD) and Parkinson's disease (PD). Herein, we investigated the frequency of GCH1 mutations and clinical symptoms in patients with clinically diagnosed PD and DRD. We used the Sanger method to screen entire exons in 268 patients with PD and 26 patients with DRD, with the examinations of brain magnetic resonance imaging scans, striatal dopamine transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans. We identified 15 patients with heterozygous GCH1 mutations from seven probands and five sporadic cases. The prevalence of GCH1 mutations in probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value < 0.0001). The onset age tends to be different between PD and DRD patients: 35.4 ± 25.3 and 16.5 ± 13.6, respectively (average ± SD; p = 0.08). Most of the patients were women (14/15). Dystonia was common symptom, and dysautonomia and cognitive decline were uncommon in our PD and DRD. All patients presented mild parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD and three of five PD presented normal heart-to-mediastinum ratio on MIBG myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal densities of dopamine transporter. Our findings elucidated the clinical characteristics of PD and DRD patients due to GCH1 mutations. PD patients with GCH1 mutations also had different symptoms from those seen in typical PD. The patients with GCH1 mutations had heterogeneous clinical symptoms.
DOI	10.1007/s00415-018-8930-8
PMID	29948246