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Fragile X mental retardation 1
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FMR1 (fragile X mental retardation 1) is a human gene that provides instructions to make a protein called fragile X mental retardation 1, or FMRP. This protein is normally made in many tissues, especially in the brain and testes. It may play a role in the development of connections (synapses) between nerve cells in the brain, where cell-to-cell communication occurs. The connections between nerve cells can change and adapt over time in response to experience (a characteristic called synaptic plasticity). FMRP may help regulate synaptic plasticity, which is important for learning and memory.
Researchers believe that FMRP acts as a shuttle within cells by carrying molecules called messenger RNA (mRNA), which contain information for making proteins. FMRP carries mRNA molecules from the nucleus to areas of the cell where proteins are assembled. Some of these mRNA molecules may be important for the function of nerve cells.
One region of the FMR1 gene has a particular sequence of 3 DNA bases, CGG, that is repeated a number of times. (Bases are the building blocks of DNA.) This region is called a trinucleotide repeat. In most people, the number of CGG repeats ranges from fewer than 10 to about 40.
Fragile X syndrome: Almost all cases of fragile X syndrome are caused by expansion of the CGG trinucleotide repeat in the FMR1 gene. In these cases, CGG is abnormally repeated from 200 to more than 1,000 times, which makes this region of the gene unstable. As a result, the FMR1 gene is turned off (silenced) and does not make any protein. Without adequate FMRP, severe learning problems or mental retardation and the other features of fragile X syndrome can develop.
Fewer than 1 % of all cases of fragile X syndrome are caused by mutations that delete part or all of the FMR1 gene or change one of the building blocks (amino acids) in FMRP. These mutations disrupt the 3-dimensional shape of FMRP or prevent any protein from being produced, leading to the signs and symptoms of fragile X syndrome.
A CGG sequence in the FMR1 gene that is repeated about 55 to 200 times is described as a premutation expansion. Men, and probably some women, with this premutation do not have fragile X syndrome, but are at increased risk of developing a disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS is characterized by progressive problems with movement (ataxia), tremor, memory loss, loss of sensation in the lower extremities (peripheral neuropathy) and mental and behavioral changes. The disorder usually develops late in life.
Although most men and women with the premutation are intellectually normal, some of these individuals have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression. About 20 % of women who carry a premutation expansion in the FMR1 gene experience premature ovarian failure (POF). POF is a loss of ovarian function in women younger than age 40, which can result in infertility (the inability to conceive a child).
Researchers have found that some children with a premutation expansion in the FMR1 gene have learning disabilities, mental retardation, or disorders in the autism spectrum (developmental disorders that affect communication and social interaction).
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