The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1

被引：17

作者：

Hayashida, Aris ^{[1
]}

Li, Yuanzhe ^{[1
]}

Yoshino, Hiroyo ^{[2
]}

Daida, Kensuke ^{[1
]}

Ikeda, Aya ^{[1
]}

Ogaki, Kotaro ^{[1
]}

Fuse, Atsuhito ^{[1
]}

Mori, Akio ^{[1
]}

Takanashi, Masashi ^{[1
]}

Nakahara, Toshiki ^{[3
]}

Yoritaka, Asako ^{[4
]}

Tomizawa, Yuji ^{[3
]}

Furukawa, Yoshiaki ^{[3
]}

Kanai, Kazuaki ^{[1
,5
]}

Nakayama, Yoshiaki ^{[6
]}

Ito, Hidefumi ^{[6
]}

Ogino, Mieko ^{[7
]}

Hattori, Yuko ^{[8
]}

Hattori, Tatsuya ^{[8
]}

Ichinose, Yuta ^{[9
]}

Takiyama, Yoshihisa ^{[9
]}

Saito, Tsukasa ^{[10
]}

Kimura, Takashi ^{[10
]}

Aizawa, Hitoshi ^{[11
]}

Shoji, Hiroshi ^{[12
]}

Mizuno, Yuri ^{[13
]}

Matsushita, Takuya ^{[13
]}

Sato, Mitsuto ^{[14
]}

Sekijima, Yoshiki ^{[14
]}

Morita, Masayo ^{[15
]}

Iwasaki, Akio ^{[16
]}

Kusaka, Hirofumi ^{[17
]}

Tada, Mikiko ^{[18
]}

Tanaka, Fumiaki ^{[18
]}

Sakiyama, Yusuke ^{[19
]}

Fujimoto, Takeshi ^{[20
]}

Nagara, Yuko ^{[21
]}

Kashihara, Kenichi ^{[22
]}

Todo, Hiroyuki ^{[23
]}

Nakao, Kouichi ^{[24
]}

Tsuruta, Kazuhito ^{[24
]}

Yoshikawa, Masaaki ^{[25
]}

Hara, Hideo ^{[25
]}

Yokote, Hiroaki ^{[26
]}

Murase, Nagako ^{[27
]}

Nakamagoe, Kiyotaka ^{[28
]}

Tamaoka, Akira ^{[30
]}

Takamiya, Motonori ^{[29
]}

Morimoto, Nobutoshi ^{[29
]}

Nokura, Kazuya ^{[30
]}

机构：

[1] Juntendo Univ, Dept Neurol, Sch Med, Tokyo, Japan

[2] Juntendo Univ, Res Inst Dis Old Age, Grad Sch Med, Tokyo, Japan

[3] Juntendo Tokyo Koto Geriatr Med Ctr, Dept Neurol, Tokyo, Japan

[4] Juntendo Univ, Dept Neurol, Koshigaya Hosp, Saitama, Japan

[5] Fukushima Med Univ, Dept Neurol, Fukushima, Japan

[6] Wakayama Med Univ, Dept Neurol, Wakayama, Wakayama Prefec, Japan

[7] Int Univ Hlth & Welf, Sch Med, Off Med Educ, Chiba, Japan

[8] Honmachi Neurol Clin, Nagoya, Aichi, Japan

[9] Univ Yamanashi, Dept Neurol, Yamanashi, Japan

[10] Natl Hosp Org Asahikawa Med Ctr, Dept Neurol, Asahikawa, Hokkaido, Japan

[11] Tokyo Med Univ, Dept Neurol, Tokyo, Japan

[12] St Marys Hosp, Div Neurol, Fukuoka, Japan

[13] Kyushu Univ, Neurol Inst, Grad Sch Med Sci, Dept Neurol, Fukuoka, Japan

[14] Shinshu Univ, Dept Med Neurol & Rheumatol, Sch Med, Matsumoto, Nagano, Japan

[15] Jikei Univ, Dept Neurol, Katsushika Med Ctr, Tokyo, Japan

[16] Dokkyo Med Univ, Dept Neurol, Mibu, Tochigi, Japan

[17] Kansai Med Univ, Dept Neurol, Osaka, Japan

[18] Yokohama City Univ, Dept Neurol & Stroke Med, Grad Sch Med, Yokohama, Kanagawa, Japan

[19] Kagoshima Univ, Dept Neurol & Geriatr, Grad Sch Med & Dent Sci, Kagoshima, Japan

[20] Sasebo City Gen Hosp, Dept Neurol, Nagasaki, Japan

[21] Nagara Clin, Fukuoka, Japan

[22] Okayama Kyokuto Hosp, Dept Neurol, Okayama, Japan

[23] Osaka Univ, Grad Sch Med, Dept RNA Biol & Neurosci, Osaka, Japan

[24] Junwakai Mem Hosp, Brain & Nerve Ctr, Miyazaki, Japan

[25] Saga Univ, Div Neurol, Dept Internal Med, Fac Med, Saga, Japan

[26] Nitobe Mem Nakano Gen Hosp, Dept Neurol, Tokyo, Japan

[27] Natl Hosp Org Nara Med Ctr, Dept Neurol, Nara, Japan

[28] Univ Tsukuba, Div Clin Med, Dept Neurol, Fac Med, Ibaraki, Japan

[29] Kagawa Prefectural Cent Hosp, Dept Neurol, Takamatsu, Kagawa, Japan

[30] Fujita Hlth Univ, Bantane Hosp, Dept Neurol, Toyoake, Aichi, Japan

来源：

NEUROBIOLOGY OF AGING | 2021年 / 97卷

基金：

日本学术振兴会;

关键词：

Parkinson's disease; PINK1; Heterozygous variants; Digenic variants; EARLY-ONSET PARKINSONISM; LEWY BODY; MYOCARDIAL SCINTIGRAPHY; DIAGNOSTIC-CRITERIA; GENETIC-VARIATION; MUTATIONS; PROTEIN; LOCALIZATION; DEMENTIA; SERVER;

D O I：

10.1016/j.neurobiolaging.2020.06.017

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [I-123] meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：146.e1 / 146.e13

页数：13

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