RESEARCH OBJECTIVE: Young-onset Parkinson's disease (YOPD), defined by symptom onset at or before 50 years of age, has a strong genetic component. The mutation spectra vary markedly across ethnic groups. However, YOPD among the Hakka, a subgroup of the Han Chinese ethnicity, remains uncharacterized. We investigated the genetic and clinical profiles of YOPD in the Hakka population of western Fujian. MATERIALS AND METHODS: A total of 33 unrelated patients with YOPD were included in the study. All patients underwent whole exome sequencing (WES) to screen all known Parkinson's disease (PD)-related genes. Patients with a family history also received a spinocerebellar ataxia (SCA) gene panel test. If the SCA gene panel test result was negative, multiplex ligation-dependent probe amplification (MLPA) for eight genes including DJ-1, ATP13A2, PINK1, UCHL1, SNCA, LRRK2, PRKN, and GCH1 was performed. Potential pathogenic variants were confirmed by Sanger sequencing, and both the genetic spectrum and clinical characteristics of patients with YOPD were analyzed. RESULTS: After variant filtering, six variants in four YOPD-related genes were identified in four unrelated patients. Of these patients, two harbored pathogenic ATXN2 repeat expansions. Four variants in VPS13C and PRKN, along with an SNCA exon 1-6 duplication, were classified as variants of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) criteria. A considerable proportion of patients harbored risk variants in LRRK2. Furthermore, nine unrelated patients harbored nine variants within six susceptibility genes associated with YOPD, including EIF4G1, COQ2, TENM4, NR4A2, UQCRC1, and GBA1. CONCLUSION: This study is the first to analyze the genetic spectrum and clinical characteristics of patients with YOPD in the Hakka population of western Fujian Province. Genetic testing of known pathogenic genes in patients with YOPD can facilitate more accurate diagnosis.