London: The gene responsible for a brain disorder may be more common than previously believed, a new study has revealed.
The researchers identified 14 different mutations in the gene CSF1R that lead to development of hereditary diffuse leukoencephalopathy with spheroids (HDLS).
This is a devastating disorder of the brain’s white matter that leads to death between ages 40 and 60. People who inherit the abnormal gene always develop HDLS. Until now, a definite diagnosis of HDLS required examination of brain tissue at biopsy or autopsy.
The finding is important because the researchers suspect that HDLS is more common than once thought and a genetic diagnosis will now be possible without need for a brain biopsy or autopsy.
According to the study’s senior investigator, neurologist Zbigniew K. Wszolek, M.D., a significant number of people who tested positive for the abnormal gene in this study had been diagnosed with a wide range of other conditions. These individuals were related to a patient known to have HDLS, and so their genes were also examined.
“Because the symptoms of HDLS vary so widely — everything from behavior and personality changes to seizures and movement problems — these patients were misdiagnosed as having either schizophrenia, epilepsy, frontotemporal dementia, Parkinson’s disease, multiple sclerosis, stroke, or other disorders,” said Dr. Wszolek.
“Many of these patients were therefore treated with drugs that offered only toxic side effects.”
“Given this finding, we may soon have a blood test that can help doctors diagnose HDLS, and I predict we will find it is much more common than anyone could have imagined.”
In this study, which included 38 researchers from 12 institutions in five countries, the study’s first author, Rosa Rademakers, Ph.D., led the effort to find the gene responsible for HDLS.
Her laboratory studied DNA samples from 14 families in which at least one member was diagnosed with HDLS and compared these with samples from more than 2,000 disease-free participants.
The gene was ultimately found using a combination of traditional genetic linkage studies and recently developed state-of-the art sequencing methods.
Most family members studied — who were found to have HDLS gene mutations — were not diagnosed with the disease, but with something else, thus emphasizing the notion that HDLS is an underdiagnosed disorder.
“With no other disease have we found so many affected families so quickly,” said Dr. Wszolek.
“That tells me this disease is not rare, but quite common,” he added.
The study has been published in the online issue of Nature Genetics.