Scientists have identified several new genetic mutations linked to a rare neurodegenerative disease called CSF1R-related disorder (CSF1R-RD). The disease is gaining recognition as the use of genetic testing becomes more routine, and more patients are tested for genetic mutations. The disease causes cognitive decline, memory loss, personality changes, depression, anxiety, and a reduction of inhibition.
The condition was first described in 1936, and it's been given several other names as researchers have learned more about it over the years, like hereditary diffuse leukoencephalopathy with spheroids (HDLS), or adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Now, these conditions are diagnosed as CSF1R-RD, which is described as either early- or late-onset when patients are under or over 18 years old, respectively.
Mutations in the CSF1R gene have been identified as the cause of the disease, and there are now about 200 genetic mutations that are linked to the disorder. A new study reported in Neurology Genetics has identified fifteen CSF1R mutations or variants in nineteen patients. Five of these mutations are novel, and can help improve diagnostic tests for the disease.
"This study contributes to the overall understanding of the inheritance and global prevalence of rare neurodegenerative conditions in people with and without familial history of the disease," said senior study author Zbigniew Wszolek, MD, a neurologist and clinical neurophysiologist at Mayo Clinic. "The discovery will allow scientists to target disease-modifying treatments specific to these mutations of the CSF1R gene."
As more mutations in the CSF1R gene are identified, it can help improve personalized treatments for the disease. There are people who carry mutations in the CSF1R gene but do not have the disease, which suggests that environmental influences may play a role in who may carry mutations and also show symptoms. The study authors also noted that there are also medications that can help prevent symptoms in carriers of CSF1R mutations, such as anti-inflammatory steroids.
Wszolek added that the symptoms of CSF1R-RD may sometimes mimic other conditions, and genetic variants can complicate those diagnoses. Diagnostic criteria should be updated, along with treatment recommendations, said Wszolek.
More research into the characteristics of symptomatic and asymptomatic carriers will also be needed, the team noted.
Sources: Mayo Clinic, Neurology Genetics