AUTHOR=Hua Ping , Zhao Yuwen , Zeng Qian , Li Lanting , Ren Jingru , Guo Jifeng , Tang Beisha , Liu Weiguo 

TITLE=Genetic Analysis of Patients With Early-Onset Parkinson’s Disease in Eastern China

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.849462

DOI=10.3389/fnagi.2022.849462

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Genetic factors play an important role in the pathogenesis of early-onset Parkinson’s disease (EOPD). To date, more than 20 pathogenic genes associated with Parkinson’s disease (PD) have been identified. This study aims to explore the mutation spectrum of EOPD and the clinical characteristics of mutation carriers in eastern China.</p></sec><sec><title>Methods</title><p>We recruited 155 unrelated EOPD patients, including 8 familial and 147 sporadic EOPD (age at onset ≤ 50 years). Overall, 24 known PD-associated genes were detected by whole exome sequencing and multiplex ligation-dependent probe amplification (MLPA) from patient samples. The genetic and clinical characteristics of pathogenic/likely pathogenic (P/LP) loci in this cohort were analyzed.</p></sec><sec><title>Results</title><p>Overall, 14 (9.03%) patients were detected with P/LP variants distributed in seven genes. The most frequent mutation occurred in <italic>PRKN</italic> (7/155, 4.52%), followed by <italic>LRRK2</italic> (2/155, 1.29%), <italic>SNCA</italic>, <italic>CHCHD2</italic>, <italic>TMEM230</italic>, <italic>DNAJC13</italic> and <italic>PLA2G6</italic> (1/155, 0.64%, respectively). Exon rearrangement mutations accounted for 57.9% (11/19) of all mutations in <italic>PRKN</italic>. Four novel variants were detected: c.14T &gt; C (p.M5T) in <italic>SNCA</italic>, c.297C &gt; A (p.Y99X) in <italic>CHCHD2</italic>, c.2578C &gt; T (p.R860C) in <italic>DNAJC13</italic> and c.4C &gt; T (p.Q2X) in <italic>TMEM230</italic>. We found the first case of <italic>LRRK2</italic> c.6055G &gt; A (p.G2019S) mutation in Chinese population. The median onset age of patients with P/LP mutations in autosomal recessive genes (<italic>PRKN</italic> and <italic>PLA2G6</italic>) was about 18.0 years earlier than patients without mutation. The proportion of patients with mutations were 63.64%, 27.03% and 9.68% when patients were stratified according to the age of onset at ≤ 30, ≤ 40 and ≤ 50 years, respectively.</p></sec><sec><title>Conclusion</title><p>Early-onset Parkinson’s disease patients from eastern China present a regional specific mutation spectrum. Analysis of larger patient cohorts is required to support these findings, and mechanistic studies of the four novel missense/non-sense mutations will clarify their role in the pathogenicity of EOPD.</p></sec>