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Ryuya Kumazawa, MD; Hiroyuki Tomiyama, MD; Yuanzhe Li, MD; Yoko Imamichi; Manabu Funayama, PhD; Hiroyo Yoshino, BS; Fusako Yokochi, MD, PhD; Toshihiro Fukusako, MD, PhD; Yasushi Takehisa, MD; Kenichi Kashihara, MD; Tomoyoshi Kondo, MD, PhD; Bulent Elibol, MD, PhD; Sevasti Bostantjopoulou, MD; Tatsushi Toda, MD, PhD; Hirohide Takahashi, MD; Fumihito Yoshii, MD, PhD; Yoshikuni Mizuno, MD; Nobutaka Hattori, MD, PhD

Arch Neurol. 2008;65(6):802-808.

Objectives  To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations.

Design  Retrospective clinical and genetic review.

Setting  University hospital.

Patients  We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries.

Results  We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations.

Conclusions  Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.

Author Affiliations: Department of Neurology (Drs Kumazawa, Tomiyama, Li, and Hattori and Ms Imamichi), and Research Institute for Diseases of Old Age (Drs Funayama and Mizuno and Ms Yoshino), Juntendo University School of Medicine, Tokyo, Japan; Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan (Dr Yokochi); Department of Neurology, Yamaguchi Grand Medical Center, Yamaguchi, Japan (Dr Fukusako); Department of Neurology, Graduate School of Medicine and Dentistry Okayama University, Okayama, Japan (Dr Takehisa); Department of Neurology, Okayama Kyokuto Hospital, Okayama, Japan (Dr Kashihara); Department of Neurology, Wakayama Medical University, Wakayama, Japan (Dr Kondo); Department of Neurology, Institute of Neurological Sciences and Psychiatry, Hacettepe University School of Medicine, Ankara, Turkey (Dr Elibol); Third University Department of Neurology, G. Papanikolaou Hospital, Thessaloniki, Greece (Dr Bostantjopoulou); Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama, Japan (Drs Toda and Hattori); and Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan (Drs Takahashi and Yoshii).

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