Genetics of Parkinson's disease: Dominant forms and GBA

Abstract

Parkinson's disease (PD) accounts for a significant burden on modern society, with an increasingly rapid growth in cases. Variants of several genes have been linked to the risk of developing the disease (e.g., the GBA gene). Other genes have been associated with autosomal dominant (e.g., SNCA, LRRK2, VPS35) and autosomal recessive PD (e.g., PRKN, PINK1, DJ-1). Such genes as 13A2, FBXO7, PLA2G6, SYNJ1, and DNAJC6 are associated with recessive forms displaying early onset, greater severity, and atypical characteristics. The genetic study of PD has clinical implications, shedding light on the underlying molecular mechanisms and potential therapeutic targets. This article presents a brief review of the molecular and genetic mechanisms and the phenotype–genotype relationship of GBA and other genes associated with autosomal dominant monogenic PD. Resumen: The prevalence of Parkinson disease (PD) has increased, representing a significant burden for modern society. Pathogenic variants in diverse genes have been related to the risk of PD (e.g., GBA). Specific pathogenic variants in several genes are causative of autosomal dominant PD (i.e., SNCA, LRRK2, VPS35) or autosomal recessive PD (i.e., PRKN, PINK1, DJ-1). Besides, genes like ATP13A2, FBXO7, PLA2G6, SYNJ1, and DNAJC6, are related to early-onset recessive parkinsonism, usually with a more severe progression and atypical features. PD genetics help in the understanding of the underlying molecular mechanism and the identification of potential therapeutic targets.This article presents a brief overview of molecular mechanisms and genotypephenotype relation of autosomal-dominant and GBA-related PD.

Keywords

• Enfermedad de Parkinson
• Genética
• GBA
• SNCA
• LRRK2
• VPS35