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Familial forms of Parkinson’s disease

These represent around 5% of all cases, are said to be monogenic and are hereditary.

To date, 13 genes have been identified as carrying 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 therefore carrying the genetic mutation will have a 50% risk of developing the disease.

The SNCA gene codes for α-synuclein, the protein that makes up the protein clusters seen in dopaminergic neurons during the course of the disease.

Genetic factors in Parkinson’s disease

The LRRK2 and VPS35 genes, which code for proteins with multiple functions in cells, particularly neurons.

The CHCHD2 and EIF4G1 genes, involved in rare cases, which code for transcription factors.

Transmission can also be recessive, in which case a child born to two healthy carriers of the mutation will have a 25% risk of developing the disease.

These genes are mainly responsible for the early forms of Parkinson’s disease that develop in young people.

The PARKIN, PINK1, DJ1 and FBX07, ATP13A2 and VPS13C genes are involved in the functions of the mitochondria, an organelle whose role is to supply the energy required by the cell for normal functioning.

The DNAJC6 genes play an essential role in synaptic transmission, enabling communication between neurons.

The PLA2G6 gene is involved in the regulation of intracellular iron.

At the Paris Brain Institute

Researchers from the team led by Olga CORTI, INSERM researcher, and Professor Jean-Christophe CORVOL, neurologist (AP-HP and Sorbonne University) are working on projects to identify mutated genes involved in Parkinson’s disease. Suzanne LESAGE’s work in 2016 led to the identification of mutations in the VSP13C gene, which is recessively inherited and causes early and very severe forms of Parkinson’s disease. This work has also revealed 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 hereditary forms. Parkinson’s disease is said to be multifactorial, occurring in genetically predisposed individuals after exposure to one or more environmental factors.

For several years now, a number of environmental and genetic factors have been identified as increasing or decreasing the risk of developing Parkinson’s disease.

While smoking and caffeine appear in studies to be protective factors against the development of the disease, pesticides, diabetes, body mass index and cholesterol have not been conclusively associated with an increased risk of developing the disease, despite a great deal of research.

There is evidence of an association between depression and Parkinson’s disease, but it is difficult to draw conclusions about the nature of this relationship. Is depression a precursor of Parkinson’s disease, or do the two diseases have a common origin?

At the Institut du Cerveau

From a genetic point of view, a very recent systematic screening study of the human genome in which the team of Olga CORTI, INSERM researcher, and Professor Jean-Christophe CORVOL, neurologist (AP-HP and Sorbonne University) took part, carried out on a population of 37,688 patients and 1.4 million controls, identified 90 polymorphisms associated with an increased risk of developing the disease. The majority of these polymorphisms could have an influence on genes involved in brain function.