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

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The identified clinical features of Parkinson’s disease in homo-, heterozygous and digenic variants of PINK1
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.neurobiolaging.2020.06.017
Arisa Hayashida ₁ , Yuanzhe Li ₁ , Hiroyo Yoshino ₂ , Kensuke Daida ₁ , Aya Ikeda ₁ , Kotaro Ogaki ₁ , Atsuhito Fuse ₁ , Akio Mori ₁ , Masashi Takanashi ₁ , Toshiki Nakahara ₃ , Asako Yoritaka ₄ , Yuji Tomizawa ₃ , Yoshiaki Furukawa ₃ , Kazuaki Kanai ₅ , Yoshiaki Nakayama ₆ , Hidefumi Ito ₆ , Mieko Ogino ₇ , Yuko Hattori ₈ , Tatsuya Hattori ₈ , Yuta Ichinose ₉ , Yoshihisa Takiyama ₉ , Tsukasa Saito ₁₀ , Takashi Kimura ₁₀ , Hitoshi Aizawa ₁₁ , Hiroshi Shoji ₁₂ , Yuri Mizuno ₁₃ , Takuya Matsushita ₁₃ , Mitsuto Sato ₁₄ , Yoshiki Sekijima ₁₄ , Masayo Morita ₁₅ , Akio Iwasaki ₁₆ , Hirofumi Kusaka ₁₇ , Mikiko Tada ₁₈ , Fumiaki Tanaka ₁₈ , Yusuke Sakiyama ₁₉ , Takeshi Fujimoto ₂₀ , Yuko Nagara ₂₁ , Kenichi Kashihara ₂₂ , Hiroyuki Todo ₂₃ , Kouichi Nakao ₂₄ , Kazuhito Tsuruta ₂₄ , Masaaki Yoshikawa ₂₅ , Hideo Hara ₂₅ , Hiroaki Yokote ₂₆ , Nagako Murase ₂₇ , Kiyotaka Nakamagoe ₂₈ , Akira Tamaoka ₂₈ , Motonori Takamiya ₂₉ , Nobutoshi Morimoto ₂₉ , Kazuya Nokura ₃₀ , Tetsuharu Kako ₃₀ , Manabu Funayama ₃₁ , Kenya Nishioka ₁ , Nobutaka Hattori ₃₁

Affiliation

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan.
Department of Neurology, Juntendo University Koshigaya Hospital, Saitama, Japan.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Department of Neurology, Fukushima Medical University, Fukushima, Japan.
Department of Neurology, Wakayama Medical University, Wakayama Prefecture, Japan.
International University of Health and Welfare, School of Medicine, Office of Medical Education, Chiba, Japan.
Honmachi Neurological Clinic, Aichi, Japan.
Department of Neurology, University of Yamanashi, Yamanashi, Japan.
Department of Neurology, National Hospital Organization Asahikawa Medical Center, Hokkaido, Japan.
Department of Neurology, Tokyo Medical University, Tokyo, Japan.
Division of Neurology, St. Mary's Hospital, Fukuoka, Japan.
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
Department of Neurology, Jikei University Katsushika Medical Center, Tokyo, Japan.
Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
Department of Neurology, Kansai Medical University, Osaka, Japan.
Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Neurology, Sasebo City General Hospital, Nagasaki, Japan.
Nagara Clinic, Fukuoka, Japan.
Department of Neurology, Okayama Kyokuto Hospital, Okayama, Japan.
Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.
Brain and Nerve Center, Junwakai Memorial Hospital, Miyazaki, Japan.
Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan.
Department of Neurology, Nitobe Memorial Nakano General Hospital, Tokyo, Japan.
Department of Neurology, National Hospital Organization Nara Medical Center, Nara, Japan.
Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Neurology, Kagawa Prefectural Central Hospital, Kagawa, Japan.
Department of Neurology, Fujita Health University, Bantane Hospital, Aichi, Japan.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

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.

中文翻译：

在 PINK1 的纯合、杂合和双基因变异中确定的帕金森病临床特征

为了研究帕金森病 (PD) 患者中磷酸酶和张力蛋白同源物诱导的推定激酶 1 (PINK1) 变异的患病率和基因型-表型相关性，我们分析了 1700 名患者（842 名家族性 PD 和 858 名来自日本的散发性 PD 患者）。我们使用 Sanger 测序和 Ion Torrent 系统的目标测序筛选了 PINK1 的整个外显子和外显子-内含子边界。我们鉴定了 30 名杂合变异患者、3 名纯合变异患者和 3 名 PINK1-PRKN 双基因变异患者。纯合变异患者的发病年龄明显低于杂合变异患者。50 岁及以下的家族性 PD 和散发性 PD 患者的杂合变异等位基因频率没有差异。[123I] 间碘苄基胍 (MIBG) 心肌闪烁扫描表明，一半携带 PINK1 杂合变异体的患者心脏与纵隔的比率降低 (12/23)。我们的研究结果强调了 PINK1 变体对 50 岁及以下患者的 PD 发病的重要性，以及 PINK1 变体患者的广泛临床症状。

更新日期：2021-01-01

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