By studying family members suspected of having Alzheimer’s disease, researchers at Washington University School of Medicine in St. Louis have identified a gene that causes a rare disorder highlighted by memory loss and motor impairments, and that leads to an early death.
The condition, known as Kufs disease, strikes middle-aged adults, but related forms also affect children and infants. Scientists say their discovery paves the way to development of a genetic test for Kufs and therapies to treat dementia, which is a hallmark of Kufs and of other neurodegenerative conditions, such as Alzheimer’s disease.
The research is reported online in the journal PLoS ONE.
The investigators found variations in the DNAJC5 gene were responsible for Kufs disease. The gene has not been associated with any human disease previously. It plays a role in transmitting signals in the brain between the nerve-cell junctions known as synapses.
What caught our attention is that synaptic dysfunction underlies other forms of dementia,” says first author Bruno Benitez, MD. “We think this Kufs-causing gene may open up a new avenue of research for these kinds of disorders because it may provide new information about dementia in general. That’s why we think this discovery could have implications beyond this rare disease.”
Kufs disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which affect two to four out of every 100,000 newborns worldwide. Kufs disease makes up fewer than 10 percent of those cases and affects mainly adults, but it can strike individuals from 6 to 60, and it is invariably fatal. Other related disorders, such as Batten disease and Jansky-Sielschowsky disease, affect children and infants, respectively. Most NCLs are inherited from parents as a recessive trait.
The study involved two Kufs disease patients from the same family who originally came to Washington University’s Alzheimer’s Disease Research Center because their memory problems were thought to be Alzheimer’s-related.
Benitez is a postdoctoral research associate in the laboratory of Carlos Cruchaga, PhD, assistant professor of psychiatry. The two worked together to identify genetic mutations that contribute to the illness.
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