A global study that determines the frequency and type of genetic variants that cause the disease
Researchers from the neurodegenerative diseases group of IDIVAL and the Neurology Service of HUMV, led by Dr. Jon Infante, have participated in an international study carried out in 16 countries and on 12,580 patients with Parkinson’s disease.
Although the cause of Parkinson’s disease is not genetic in most cases, it is estimated that around 10% may be caused by mutations in various genes. However, the knowledge we have regarding the spectrum and frequency of different genetic mutations globally is limited and biased. At a time when the first clinical trials with therapies targeting specific genetic subtypes of Parkinson’s have been initiated, a major obstacle to the conduct of these trials is that many Parkinson’s patients do not know whether their disease is caused by any of these genes.
The Rostock Parkinson’s disease study (ROPAD), published in the prestigious journal Brain, is an observational clinical study aimed at determining the frequency and spectrum of genetic variants contributing to PD in a large international cohort. Variants in 50 genes were investigated in a group of 12,580 Parkinson’s disease patients from 16 countries using a next-generation sequencing panel. In total, in 1864 participants (14.8%) some gene mutation was identified, the most frequent being in the GBA1 (10.4%), LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) genes or a combination of mutations in two genes in two genes (∼0.2%). In patients with age of onset less than 50 years the frequency of mutations was 19.5% and in those who also had a family history it rose to 26.9%.
In the emerging era of gene-targeted clinical trials, the finding that ∼15% of patients harbor potentially actionable genetic variants offers an important perspective to affected individuals and their families, and underscores the need for genetic testing in patients with Parkinson’s disease.
The neurodegenerative diseases group of IDIVAL has a long history of research in the field of Parkinson’s disease genetics, having contributed to define the genetic epidemiology of a genetic subtype of Parkinson’s disease, associated with variants in the LRRK2 gene, particularly frequent in Cantabria. Through different studies this group has contributed to the identification of biomarkers of the presymptomatic stages of the disease.
Reference:
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Cover photo: IDIVAL neurodegenerative diseases group.
