Genotype-phenotype correlation of Parkinson's disease with PRKN variants

To investigate the prevalence and genotype-phenotype correlations of parkin RBR E3 ubiquitin protein lig-ase (PRKN) variants in Parkinson's disease (PD), we first included 2,527 patients with PD. Through the de -fined selection, we enrolled 2,322 patients, including 1,204 with familial and 1,118 with sporadic PD. We identified 242 patients harboring PRKN variants, which were thought to be susceptibility factors, compris-ing 137 patients with familial and 105 with sporadic PD; among the 26 identified variants, 13 were novel. We divided our cohort into 2 groups: heterozygote (hereafter called one-allele) and homozygote or com-pound heterozygote (hereafter called two-allele). The patients with two-allele were significantly younger at onset than those with one-allele. Six families harbored the complex forms of one-and two-allele in different individuals of the same family. The presence of two-allele reflected more frequent normal val-ues of [ (123) I] metaiodobenzylguanidine myocardial scintigraphy. The log-rank test revealed an exacerbation associated with two-allele over 15 years of the disease course. The patients with PRKN variants showed specific symptoms dependent on the number of mutated alleles. (c) 2022 Elsevier Inc. All rights reserved.