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

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. •To investigate the prevalence and genotype-phenotype correlations of PINK1.•We analyzed 1700 Parkinson's disease (PD) including 842 familial and 858 sporadic.•We identified 30 patients with hetero-, 3 with homozygous, and 3 with PRKN-PINK1.•Heterozygote was frequently seen in the familial and sporadic PD with young-onset.•The age at onset dependents on the number of affected alleles.