Abstract
A loss-of-function variant in Lin-28 Homolog A gene (LIN28A p. R192G, rs558060339) has been identified in two East Asian ancestry patients with early-onset PD (EOPD). Functional studies revealed that such a variant could lead to developmental defects and PD-related phenotype, and the phenotypes could be rescued after correction of the variant. The aim of the study was to screen the variants of LIN28A in Chinese patients with EOPD. A total of 682 EOPD patients were sequenced with whole exome sequencing and the coding and flanking region of LIN28A were analyzed. We identified a rare coding variant, p. P182L, of LIN28A in a Chinese patient with EOPD. Moreover, we also found a 3′-UTR polymorphism (rs4659441) to be associated with an increased risk for PD. However, our rare variant burden analysis did not support a role for LIN28A as a major causal gene for PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease with a complex spectrum of etiologies including aging, environmental factors, and genetic causes (Poewe et al, 2017)
A loss-of-function variant in the Lin-28 Homolog A gene (LIN28A) (p.R192G, rs558060339) was identified in two East Asian ancestry patients with early-onset PD (EOPD) (Chang et al, 2019); developmental defects and PD-related phenotype due to the variant was rescued after correction of the variant (Chang et al, 2019)
A subsequent study conducted in a large cohort of PD patients of European ancestry failed to find evidence supporting the causative role of LIN28A in PD (Diez-Fairen et al, 2021)
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease with a complex spectrum of etiologies including aging, environmental factors, and genetic causes (Poewe et al, 2017). With the development of genetic sequencing methods and bioinformatic analysis algorithms, novel PD causative genes have been extensively explored in recent years, and Lin-28 Homolog A gene (LIN28A) is one of them. Previous studies have indicated that LIN28A might play a role in the pathogenesis of PD. A loss-of-function variant in the LIN28A (p.R192G, rs558060339) was identified in two East Asian ancestry patients with early-onset PD (EOPD) (Chang et al, 2019); developmental defects and PD-related phenotype due to the variant was rescued after correction of the variant (Chang et al, 2019). A subsequent study conducted in a large cohort of PD patients of European ancestry failed to find evidence supporting the causative role of LIN28A in PD (Diez-Fairen et al, 2021).
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