Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing

Area of Science:

• Neurogenetics
• Molecular Neurology
• Human Genetics

Background:

• Monogenic forms account for 5-10% of Parkinson's disease (PD) cases.
• Investigating these genetic disorders provides crucial pathophysiological insights.
• Established genes include autosomal dominant (SNCA, LRRK2, VPS35) and recessive (PRKN, PINK1, DJ1) forms.

Purpose of the Study:

• To review genetic forms of Parkinson's disease.
• To focus on genotype, phenotype, pathophysiology, and geographic/ethnic distribution.
• To discuss recent genetic discoveries and complex parkinsonism.

Main Methods:

• Literature review of genetic forms of Parkinson's disease.
• Analysis of genotype-phenotype correlations.
• Examination of geographical and ethnic distributions of genetic variants.

Main Results:

• Discusses well-established genes (SNCA, LRRK2, VPS35, PRKN, PINK1, DJ1) and risk factors (GBA).
• Highlights genes implicated in atypical/complex parkinsonism (ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, SYNJ1).
• Identifies recently implicated genes (CHCHD2, LRP10, TMEM230, UQCRC1, VPS13C) and discusses heterozygous mutations and dual-gene effects.

Conclusions:

• Monogenic Parkinson's disease exhibits significant ethnic and geographical variability.
• Global collaborative efforts are essential for pooling patient data and identifying novel candidate genes.
• Understanding genetic underpinnings is key to advancing Parkinson's disease research and potential therapies.