A Study Provides New Genetic Understanding to Fragile X Syndrome

Investigators have advance their understanding of fragile X syndrome – the very popular identified cause of inherited intellectual disability – thanks to a sufferer with a mutation in a particular gene showing some of the disorder’s symptoms.

Generally, fragile X syndrome is triggered by the disabling of the fragile X mental retardation (FMR1) gene liable for developing a protein – fragile X mental retardation protein (FMRP). FMRP is used to control electrical signals in the human brain.

However, the sufferer evaluated in the research had only a single error in this gene and showed just two of the primary symptoms of the condition. As a outcome, the investigators were capable to evaluate a hitherto unidentified role for the gene.

Co-senior author Prof. Vitaly A. Klyachko states that “This individual case has helped us to distinct two separate features of the fragile X protein in the brain.”

“By discovering the mutation, even in just one sufferer, and connecting it to a partial set of traits, we have recognized a unique function that this gene is liable for and that is probably impaired in all individuals with fragile X.”

In accordance to the Centers for Disease Control and Prevention (CDC), it is approximated that about one in 5,000 men are born with fragile X syndrome. The problem can cause serious intellectual disability, which includes an inability to communicate. Fragile X syndrome is very probably to impact males as the FMR1 gene is on the X chromosome.

Individuals with fragile X syndrome can also experience stress and seizures, together with physical symptoms like as bigger heads or flat feet. In addition, around 35% of individuals with the condition show symptoms of autism spectrum disorders.

For the research

For the research, reported in Proceedings of the National Academy of Sciences, investigators from Washington University and Emory University School of Medicine analyzed genetic sequencing information for more than 900 men with intellectual problems but not fragile X syndrome.

Their goal was to discover mutations in the FMR1 gene that reduced FMRP but did not completely eliminate it. Only one individual was identified from the sample that had irregular FMRP, triggered by a small mutation in the FMR1 gene’s DNA code.

The individual had intellectual impairment and experienced seizures but had no physical functions that were related with fragile X syndrome, nor symptoms of autism.

After duplicating the mutation in the mouse brain cells, the investigators identified that FMRP seemed to work usually, showing that the patient’s brain cells obtained signals usually, working just as they would in healthy individuals without the problem.

“This sufferer provides a case of partial fragile X syndrome connected with mutated, instead of absent, FMRP,” states Prof. Klyachko. “As much as I know, this is the only identified case of this. It’s a unique chance to parse out the functions of FMRP. What does this mutation impair to trigger only 2 symptoms of fragile X?”

The study team then replicated the mutation in fruit flies to test and answer this issue. They identified that the mutation lead to a raise in the number of transmitters in the brain cells – challenging as it could result in a lot of signals being sent within the brain.

Conclusions

Formerly, study into fragile X syndrome has targeted on issues taking place with how and when signals are obtained in the brain, especially looking at receivers that are extremely delicate and allow in too much information.

The investigators’ results recommend that drugs recently examined as treatment for fragile X syndrome may be useless because of targeting receivers in the brain and not dealing with higher levels of signal transmission.

Prof. Klyachko’s team were capable to confirm the impact noticed in the fruit flies in mammals and link it to human disease. The enhanced number of transmitters triggered by the patient’s mutation also took place with a overall loss of FMRP.

The investigators acknowledge that there may be other issues triggered by both the mutation and fragile X syndrome, but for now this research has recognized one dysfunction that was formerly unidentified.

“The mechanisms that scientists have long thought were the whole of the issue with fragile X are obviously even now very much in play,” Prof. Klyachko notices. “But this exclusive case has permitted us to see that something different is going on.”