Listen to this story: Fragile X syndrome is a leading genetic cause of autism. About one in three people with the syndrome also has autism. But even those who do not have autism often share certain autistic traits, such as avoidance of eye contact and difficulties in social situations. Mutations in the gene FMR1, which cause fragile X syndrome, account for up to 5 percent of autism cases. For these reasons, research on fragile X can provide insights into the biology of autism and its treatment. Here is what scientists know about the mechanisms that underlie fragile X and some research angles they are pursuing. What is fragile X syndrome? What is the relationship between fragile X syndrome and autism? What causes fragile X? The expanded repeats can silence the production of a protein called FMRP. This protein serves critical functions, such as controlling the production of proteins at synapses, the junctions between neurons. The leading theory of fragile X holds that when FMRP is missing, protein synthesis can run rampant and disrupt cognitive processes. A study published last month, however, has complicated scientists’ understanding of the syndrome: It hints that loss of FMRP instead causes a dearth of proteins. What is the fragile X syndrome ‘premutation’? Some women with the premutation develop a condition called fragile X-associated primary ovarian insufficiency, which can trigger early menopause. Both men and women with the premutation may develop a condition called fragile X-associated tremor/ataxia syndrome, which causes tremors and cognitive problems. The risk of developing this condition increases with age: Estimates suggest 30 percent of affected men and 8 to 16.5 percent of affected women over age 50 have it1. The repeats of the premutation can sometimes expand in future generations to the full syndrome. The more repeats in the mother’s premutation, the greater the chance the child will have a full mutation. Some people have between 45 and 54 CGG repeats — a so-called ‘gray zone’ mutation. Little is known about the effects of this mutation, although evidence suggests it can lead to some features of fragile X-associated tremor/ataxia syndrome. Are there animal models available to study fragile X? Whether insights from the mice apply to people with the condition is unclear. The behaviors seen in mice that lack FMR1 are often inconsistent — and in many cases do not resemble those in people. For instance, the mutant mice do not show cognitive problems, one of the core features of fragile X. An animal model that faithfully mimics the syndrome would help researchers test treatments and trace the syndrome’s origins. Are there treatments for fragile X syndrome? Researchers are investigating many candidate drugs, including several that block a protein called mGluR5. Some of the candidates, such as arbaclofen and mavoglurant, have been shown to restore protein production and ease problems with learning and memory in the mutant mice. But none of the drugs has fared well in clinical trials. That may be because the trials used the wrong markers to measure the drugs’ effectiveness. Or it may because the trials involved adolescents and adults, whose brains may no longer respond to intervention. One team is testing mavoglurant in young children and using a test of language learning to measure its effectiveness. They plan to pair the drug with an intensive language intervention. Other teams are testing a drug called lovastatin, which is used to treat high cholesterol levels and has been shown to reduce seizures in fragile X mice. Researchers are also testing a drug that targets the enzyme PDE4D and seems to improve social behaviors in the mutant mice3. What are the next steps for the field? Cite this article: https://doi.org/10.53053/EVHV5906 Does autism spectrum disorder have a genetic cause?What causes autism spectrum disorder? Although the cause of ASD is known in some people and not known in others, genetics, biology, and environment are all important factors. Having older parents, a difficult birth, or infections during pregnancy are all examples of factors that might increase the risk for having ASD.
Is there a genetic gene for autism?Is there such a thing as an autism gene? Not really. There are several conditions associated with autism that stem from mutations in a single gene, including fragile X and Rett syndromes. But less than 1 percent of non-syndromic cases of autism stem from mutations in any single gene.
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