Researchers gained new insight into an inherited intellectual disability called fragile X syndrome by looking at a patient who did not suffer from it.
In patients with Fragile X Syndrome a gene is disabled, which in turn eliminates an electrical signal regulating protein causing a number of behavioral and neurological symptoms, Washington University in St. Louis reported. The patient looked at in the study had only a single error in this gene, and displayed two classic symptoms of fragile X, intellectual disability and seizures.
"This individual case has allowed us to separate two independent functions of the fragile X protein in the brain," said co-senior author Vitaly A. Klyachko, PhD, associate professor of cell biology and physiology at Washington University School of Medicine in St. Louis. "By finding the mutation, even in just one patient, and linking it to a partial set of traits, we have identified a distinct function that this gene is responsible for and that is likely impaired in all people with fragile X."
In the past most fragile X research has looked at problems with overly sensitive receivers, but these new findings suggest the condition also causes overactive transmitters that send out too much information.
"The mechanisms that researchers have long thought were the entirety of the problem with fragile X are obviously still very much in play," Klyachko said. "But this unique case has allowed us to see that something else is going on."
The findings also suggest drugs recently tested as treatments for fragile X may be ineffective because they only target the brain's receivers.
The findings were made through genetic sequencing data taken from more than 900 males with intellectual disabilities but without classic fragile X syndrome. Out of this sample they identified only one patient with abnormal FMRP (the protein associated with fragile X). The team replicated the mutation in mice's brains. They found the mutated FMRP appeared to work normally, meaning the brain cells had normal receivers.
"This single point mutation does not seem to affect the classical, well-known functions of FMRP," said Klyachko, also an associate professor of biomedical engineering. "This patient presents a case of partial fragile X syndrome associated with mutated, rather than absent, FMRP. As far as I know, this is the only known case of this. It's a unique opportunity to parse out the functions of FMRP. What does this mutation impair to cause only two symptoms of fragile X?"
The researchers noted they have not ruled out the possibility that other problems are caused by the mutation, but these findings identify at least one additional dysfunction has not been previously recognized.
The findings were published in a recent edition of the Proceedings of the National Academy of Sciences (PNAS).
