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Scientists uncover trigger for most common form of intellectual disability and autism

A new study led by Weill Cornell Medical College scientists shows that the most common genetic form of mental retardation and autism occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published in Science, also show that a drug that blocks this silencing mechanism can prevent fragile X syndrome - suggesting similar therapy is possible for 20 other diseases that range from mental retardation to multisystem failure.

Fragile X syndrome occurs mostly in boys, causing intellectual disability as well as telltale physical, behavioral and emotional traits. While researchers have known for more than two decades that the culprit behind the disease is an unusual mutation characterized by the excess repetition of a particular segment of the genetic code, they weren't sure why the presence of a large number of these repetitions - 200 or more - sets the disease process in motion.A new study led by Weill Cornell Medical College scientists shows that the most common genetic form of mental retardation and autism occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published today in Science, also show that a drug that blocks this silencing mechanism can prevent fragile X syndrome - suggesting similar therapy is possible for 20 other diseases that range from mental retardation to multisystem failure.

Fragile X syndrome occurs mostly in boys, causing intellectual disability as well as telltale physical, behavioral and emotional traits. While researchers have known for more than two decades that the culprit behind the disease is an unusual mutation characterized by the excess repetition of a particular segment of the genetic code, they weren't sure why the presence of a large number of these repetitions - 200 or more - sets the disease process in motion.

Using stem cells from donated human embryos that tested positive for fragile X syndrome, the scientists discovered that early on in fetal development, messenger RNA - a template for protein production - begins sticking itself onto the fragile X syndrome gene's DNA. This binding appears to gum up the gene, making it inactive and unable to produce a protein crucial to the transmission of signals between brain cells.

"Until 11 weeks of gestation, the fragile X syndrome gene is active - it produces its messenger RNA and protein normally. Then, all of a sudden it turns off, and stays off for the rest of the patient's lifetime, causing fragile X syndrome. But scientists have not understood why this gene gets shut off," says senior author Dr. Samie Jaffrey, a professor of pharmacology at Weill Cornell Medical College. "We discovered that the messenger RNA can jam up one strand of the gene's DNA, shutting down the gene - which was not known before.