Abstract
Defects in the α-synuclein, leucine-rich repeat kinase 2, or glucocerebrosidase genes have been regarded as essential contributors to PD. However, genetic variability of these genes with respect to early-onset PD remains poorly defined for the Chinese demographic. We aim to systematically characterize the clinical and genetic architecture of α-synuclein, leucine-rich repeat kinase 2, and glucocerebrosidase in Chinese early-onset PD patients. Whole-exome sequencing and Sanger sequencing were used to identify variants of α-synuclein, leucine-rich repeat kinase 2, and glucocerebrosidase in 662 Chinese early-onset PD patients. Haplotype and burden analyses were conducted to investigate the role of rare variants of these three genes in early-onset PD. Sixty rare variants, including 23 novel variants, were identified in 73 patients (11.0%). Frequencies of patients with rare pathogenic/likely pathogenic variants of α-synuclein, leucine-rich repeat kinase 2, and glucocerebrosidase were 0.6%, 3.0%, and 5.4%, respectively. Evidences of two founder events exclusive to Asians were identified in 2 patients with leucine-rich repeat kinase 2 p.R1441C and 3 patients with α-synuclein p.A53V. Gene-based burden analysis supported glucocerebrosida...Continue Reading
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