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	Atypical parkinsonism caused by Pro105Leu mutation of prion protein: A broad clinical spectrum.
掲載誌名	正式名：Neurology. Genetics
掲載区分	国外
巻・号・頁	2(1),e48頁
著者・共著者	Kagari Koshi Mano,Takashi Matsukawa,Jun Mitsui,Hiroyuki Ishiura,Shin-Ichi Tokushige,Yuji Takahashi,Naoko Saito Sato,Fumiko Kusunoki Nakamoto,Yaeko Ichikawa,Yu Nagashima,Yasuo Terao,Jun Shimizu,Masashi Hamada,Yoshikazu Uesaka,Genko Oyama,Go Ogawa,Jun Yoshimura,Koichiro Doi,Shinichi Morishita,Shoji Tsuji,Jun Goto
発行年月	2016/02
概要	OBJECTIVE: To delineate molecular and clinical characteristics of 3 families with PRNP P105L mutation, a variant of Gerstmann-Sträussler-Scheinker syndrome whose main motor symptoms were parkinsonism and/or involuntary movements. METHODS: The causative mutation was first determined in the affected patients of family 1 using whole-exome sequencing, and then mutational analysis was extended to families 2 and 3. The clinical features of the patients of these 3 families were summarized. Haplotype analysis was performed using high-density single nucleotide polymorphism array. RESULTS: The whole-exome sequencing revealed that the heterozygous mutation c.314C>T (p.P105L) in PRNP was the only known pathogenic mutation shared by the 3 patients of the family with autosomal dominant parkinsonism. We further identified the same mutation in patients of the other 2 families with autosomal dominant parkinsonism and/or involuntary movements. The clinical features of our patients with PRNP P105L mutation included various motor symptoms such as parkinsonism and involuntary movements in addition to progressive dementia. The clinical features in part overlapped with those of other forms of inherited prion diseases, such as fatal familial insomnia and Huntington disease-like type 1. The patients with PRNP P105L mutation shared a haplotype spanning 7.1 Mb around PRNP, raising the possibility that the mutations in the patients originated from a common founder. CONCLUSION: Most of the patients presented with parkinsonism in addition to progressive dementia. Although spastic paraparesis has been emphasized as the main clinical feature, the clinical spectrum of patients with PRNP P105L is broader than expected.
DOI	10.1212/NXG.0000000000000048
PMID	27066585