Family forms of Parkinson's disease
They represent about 5% of all cases, are so-called monogenic and are hereditary.
To date, 13 genes have been identified as carriers of disease-causing mutations.
The transmission of these genes may be dominant, in which case a child born to a parent with Parkinson’s disease and thus carrying the genetic mutation will have a 50% risk of developing the disease.
The SNCA gene that encodes α-synuclein, the protein component of protein clusters observed in dopaminergic neurons during disease.
Genetic Factors in Parkinson's Disease
The LRRK2 and VPS35 genes that encode proteins with multiple functions in cells, particularly neurons.
CHCHD2 and EIF4G1, involved in rare cases that encode transcription factors.
Transmission can also be recessive and in this case the risk for a child born from the union of two healthy carriers of the mutation will be 25% of the risk of developing the disease.
These genes are largely responsible for the early forms of Parkinson’s disease that develop in young people.
The genes PARKIN, PINK1, DJ1 and FBX07, ATP13A2 and VPS13C are involved in the functions of the mitochondria, an organelle whose role is to provide the necessary energy to the cell for normal functioning.
DNAJC6 genes play an essential role in synaptic transmission that allows communication between neurons.
The PLA2G6 gene involved in the regulation of intracellular iron.
At Paris Brain Institute
Researchers from the team of Olga CORTI, INSERM researcher and Professor Jean-Christophe CORVOL, neurologist (AP-HP and Sorbonne University) carry research projects on mutated genes involved in Parkinson’s disease. Suzanne LESAGE’s work in 2016 led to the identification of recessive transmission mutations in the VSP13C gene that cause early and severe forms of Parkinson’s disease. This work has also highlighted the role of these mutations in mitochondrial dysfunction.
Sporadic cases of Parkinson's disease
In 95% of cases, the disease occurs in a person who does not carry mutations in the genes involved in the hereditary forms. Parkinson's disease is multifactorial, occurring in individuals genetically predisposed to exposure to one or more environmental factors.
For several years, many environmental and genetic factors have been identified as increasing or decreasing the risk of developing Parkinson's disease.
While tobacco and caffeine appear to be protective factors against the development of the disease, pesticides, diabetes, body mass index, and cholesterol have not been definitively associated with an increased risk of developing the disease despite much research.
An association between depression and Parkinson's disease has been found, but it is difficult to conclude on the nature of this relationship. Is depression an early warning sign of Parkinson’s disease, or do the two diseases have a common origin?
At Paris Brain Institute
From a genetic point of view, a very recent study of systematic screening of the human genome, involving the team of Olga CORTI, INSERM researcher, and Professor Jean-Christophe CORVOL, neurologist (AP-HP and Sorbonne University), conducted on a population of 37,688 patients and 1.4 million controls, identified 90 polymorphisms associated with an increased risk of developing the disease. A majority of these polymorphisms may influence genes involved in brain function.
