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

Arisa Hayashida; Yuanzhe Li; Hiroyo Yoshino; Kensuke Daida; Aya Ikeda; Kotaro Ogaki; Atsuhito Fuse; Akio Mori; Masashi Takanashi; Toshiki Nakahara; Asako Yoritaka; Yuji Tomizawa; Yoshiaki Furukawa; Kazuaki Kanai; Yoshiaki Nakayama; Hidefumi Ito; Mieko Ogino; Yuko Hattori; Tatsuya Hattori; Yuta Ichinose; Yoshihisa Takiyama; Tsukasa Saito; Takashi Kimura; Hitoshi Aizawa; Hiroshi Shoji; Yuri Mizuno; Takuya Matsushita; Mitsuto Sato; Yoshiki Sekijima; Masayo Morita; Akio Iwasaki; Hirofumi Kusaka; Mikiko Tada; Fumiaki Tanaka; Yusuke Sakiyama; Takeshi Fujimoto; Yuko Nagara; Kenichi Kashihara; Hiroyuki Todo; Kouichi Nakao; Kazuhito Tsuruta; Masaaki Yoshikawa; Hideo Hara; Hiroaki Yokote; Nagako Murase; Kiyotaka Nakamagoe; Akira Tamaoka; Motonori Takamiya; Nobutoshi Morimoto; Kazuya Nokura; Tetsuharu Kako; Manabu Funayama; Kenya Nishioka; Nobutaka Hattori

doi:10.1016/j.neurobiolaging.2020.06.017

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

Arisa Hayashida, Yuanzhe Li, Hiroyo Yoshino, Kensuke Daida, Aya Ikeda, Kotaro Ogaki, Atsuhito Fuse, Akio Mori, Masashi Takanashi, Toshiki Nakahara, Asako Yoritaka, Yuji Tomizawa, Yoshiaki Furukawa, Kazuaki Kanai, Yoshiaki Nakayama, Hidefumi Ito, Mieko Ogino, Yuko Hattori, Tatsuya Hattori, Yuta IchinoseYoshihisa Takiyama, Tsukasa Saito, Takashi Kimura, Hitoshi Aizawa, Hiroshi Shoji, Yuri Mizuno, Takuya Matsushita, Mitsuto Sato, Yoshiki Sekijima, Masayo Morita, Akio Iwasaki, Hirofumi Kusaka, Mikiko Tada, Fumiaki Tanaka, Yusuke Sakiyama, Takeshi Fujimoto, Yuko Nagara, Kenichi Kashihara, Hiroyuki Todo, Kouichi Nakao, Kazuhito Tsuruta, Masaaki Yoshikawa, Hideo Hara, Hiroaki Yokote, Nagako Murase, Kiyotaka Nakamagoe, Akira Tamaoka, Motonori Takamiya, Nobutoshi Morimoto, Kazuya Nokura, Tetsuharu Kako, Manabu Funayama, Kenya Nishioka, Nobutaka Hattori

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Abstract

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. [¹²³I]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.

Original language	English
Pages (from-to)	146.e1-146.e13
Journal	Neurobiology of Aging
Volume	97
DOIs	https://doi.org/10.1016/j.neurobiolaging.2020.06.017
Publication status	Published - 01-2021

All Science Journal Classification (ASJC) codes

General Neuroscience
Ageing
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2020.06.017

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Hayashida, A., Li, Y., Yoshino, H., Daida, K., Ikeda, A., Ogaki, K., Fuse, A., Mori, A., Takanashi, M., Nakahara, T., Yoritaka, A., Tomizawa, Y., Furukawa, Y., Kanai, K., Nakayama, Y., Ito, H., Ogino, M., Hattori, Y., Hattori, T., ... Hattori, N. (2021). The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1. Neurobiology of Aging, 97, 146.e1-146.e13. https://doi.org/10.1016/j.neurobiolaging.2020.06.017

@article{b38b3de6fc1f4ee4ab5add1514714f3a,

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

abstract = "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. [123I]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.",

author = "Arisa Hayashida and Yuanzhe Li and Hiroyo Yoshino and Kensuke Daida and Aya Ikeda and Kotaro Ogaki and Atsuhito Fuse and Akio Mori and Masashi Takanashi and Toshiki Nakahara and Asako Yoritaka and Yuji Tomizawa and Yoshiaki Furukawa and Kazuaki Kanai and Yoshiaki Nakayama and Hidefumi Ito and Mieko Ogino and Yuko Hattori and Tatsuya Hattori and Yuta Ichinose and Yoshihisa Takiyama and Tsukasa Saito and Takashi Kimura and Hitoshi Aizawa and Hiroshi Shoji and Yuri Mizuno and Takuya Matsushita and Mitsuto Sato and Yoshiki Sekijima and Masayo Morita and Akio Iwasaki and Hirofumi Kusaka and Mikiko Tada and Fumiaki Tanaka and Yusuke Sakiyama and Takeshi Fujimoto and Yuko Nagara and Kenichi Kashihara and Hiroyuki Todo and Kouichi Nakao and Kazuhito Tsuruta and Masaaki Yoshikawa and Hideo Hara and Hiroaki Yokote and Nagako Murase and Kiyotaka Nakamagoe and Akira Tamaoka and Motonori Takamiya and Nobutoshi Morimoto and Kazuya Nokura and Tetsuharu Kako and Manabu Funayama and Kenya Nishioka and Nobutaka Hattori",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

month = jan,

doi = "10.1016/j.neurobiolaging.2020.06.017",

language = "English",

volume = "97",

pages = "146.e1--146.e13",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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Hayashida, A, Li, Y, Yoshino, H, Daida, K, Ikeda, A, Ogaki, K, Fuse, A, Mori, A, Takanashi, M, Nakahara, T, Yoritaka, A, Tomizawa, Y, Furukawa, Y, Kanai, K, Nakayama, Y, Ito, H, Ogino, M, Hattori, Y, Hattori, T, Ichinose, Y, Takiyama, Y, Saito, T, Kimura, T, Aizawa, H, Shoji, H, Mizuno, Y, Matsushita, T, Sato, M, Sekijima, Y, Morita, M, Iwasaki, A, Kusaka, H, Tada, M, Tanaka, F, Sakiyama, Y, Fujimoto, T, Nagara, Y, Kashihara, K, Todo, H, Nakao, K, Tsuruta, K, Yoshikawa, M, Hara, H, Yokote, H, Murase, N, Nakamagoe, K, Tamaoka, A, Takamiya, M, Morimoto, N, Nokura, K, Kako, T, Funayama, M, Nishioka, K & Hattori, N 2021, 'The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1', Neurobiology of Aging, vol. 97, pp. 146.e1-146.e13. https://doi.org/10.1016/j.neurobiolaging.2020.06.017

TY - JOUR

T1 - The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1

AU - Hayashida, Arisa

AU - Li, Yuanzhe

AU - Yoshino, Hiroyo

AU - Daida, Kensuke

AU - Ikeda, Aya

AU - Ogaki, Kotaro

AU - Fuse, Atsuhito

AU - Mori, Akio

AU - Takanashi, Masashi

AU - Nakahara, Toshiki

AU - Yoritaka, Asako

AU - Tomizawa, Yuji

AU - Furukawa, Yoshiaki

AU - Kanai, Kazuaki

AU - Nakayama, Yoshiaki

AU - Ito, Hidefumi

AU - Ogino, Mieko

AU - Hattori, Yuko

AU - Hattori, Tatsuya

AU - Ichinose, Yuta

AU - Takiyama, Yoshihisa

AU - Saito, Tsukasa

AU - Kimura, Takashi

AU - Aizawa, Hitoshi

AU - Shoji, Hiroshi

AU - Mizuno, Yuri

AU - Matsushita, Takuya

AU - Sato, Mitsuto

AU - Sekijima, Yoshiki

AU - Morita, Masayo

AU - Iwasaki, Akio

AU - Kusaka, Hirofumi

AU - Tada, Mikiko

AU - Tanaka, Fumiaki

AU - Sakiyama, Yusuke

AU - Fujimoto, Takeshi

AU - Nagara, Yuko

AU - Kashihara, Kenichi

AU - Todo, Hiroyuki

AU - Nakao, Kouichi

AU - Tsuruta, Kazuhito

AU - Yoshikawa, Masaaki

AU - Hara, Hideo

AU - Yokote, Hiroaki

AU - Murase, Nagako

AU - Nakamagoe, Kiyotaka

AU - Tamaoka, Akira

AU - Takamiya, Motonori

AU - Morimoto, Nobutoshi

AU - Nokura, Kazuya

AU - Kako, Tetsuharu

AU - Funayama, Manabu

AU - Nishioka, Kenya

AU - Hattori, Nobutaka

PY - 2021/1

Y1 - 2021/1

N2 - 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. [123I]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.

AB - 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. [123I]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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85088378328&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2020.06.017

DO - 10.1016/j.neurobiolaging.2020.06.017

M3 - Article

C2 - 32713623

AN - SCOPUS:85088378328

SN - 0197-4580

VL - 97

SP - 146.e1-146.e13

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

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