Researchers identify genetic mutations responsible for rare disease causing cognitive decline

A rare cause of inherited cognitive decline known as CSF1R-related disorder (CSF1R-RD) is named for mutations in the CSF1R gene, discovered by the Mayo Clinic. Memory loss occurs as the disease progresses, while early symptoms include personality changes, anxiety, depression, and loss of inhibition. Genetic testing is now more widely available, but there is no cure for the disorder.

In a new study published in Neurology GeneticsMayo Clinic researchers have identified eight new genetic mutations in patients with CSF1R-related disorders worldwide.

These findings highlight the prevalence of the disease and pave the way for future individualized treatment. The finding also suggests that genetic and environmental factors may influence the disease. For example, steroids used to treat inflammation and immune responses may reduce neuroinflammation and prevent the onset of symptoms in asymptomatic carriers of CSF1R gene mutations, the research team says.

The researchers analyzed a series of data (demographics, genotype, family history, clinical status) collected from 14 families from America, Asia, Australia and Europe. They discovered 15 mutations in the CSF1R gene, eight of which had never been reported before. There are nearly 200 known mutations associated with this disease.

“This study contributes to the overall understanding of the inheritance and global prevalence of rare neurodegenerative diseases in people with and without a family history of the disease,” said Zbigniew Wszolek, MD, lead author of the study, a neurologist and clinical neurophysiologist at Mayo Clinic. “This discovery will allow scientists to target disease-modifying treatments specific to these CSF1R mutations.”

Genetic variations can complicate diagnosis of the disease because symptoms can mimic those of other conditions, Dr. Wszolek says. Accurate diagnosis and medical management of the disease require up-to-date diagnostic criteria and treatment options, he adds.

The research team believes that further studies are needed to examine asymptomatic and symptomatic carriers of CSF1R mutations to better understand the disease. They note that the knowledge gained from this research will improve genetic counseling, guide the development of therapeutic interventions, and improve prediction of disease risk.

Dr. Wszolek and his research team discovered the CSF1R gene in 2011. One of the team’s previous studies on CSF1R-related disorder, also known as CSF1R-related leukoencephalopathy, looked at a disease-modifying treatment.