Fragile X Syndrome (cont.)
In this Article
What keeps the FMR1 gene from producing FMRP in Fragile X syndrome?
The information for making a protein has two parts: the introduction, and the instructions for the protein itself. Scientists call the introduction "the promoter region" of the gene because of its role in starting the protein-building process. (For a more complete description of how proteins are made and the parts of a cell involved in making a protein, see the Human cells 101 section.)
The promoter region of the FMR1 gene contains repeats of a specific sequence (cytosine-guanine-guanine or CGG-see the Human cells 101 section for specific information about the CGG sequence) that, when normal, controls the activity level of the gene in building FMRP.
The number of repeated sequences in the promoter region varies from person to person. Most people who do not have Fragile X have between six and 40 CGG repeats,3 with the average being about 30 repeats in the promoter region.4
However, in a mutated FMR1 gene, the promoter may have hundreds of repeated sequences.
The larger number of repeats (more than 200) inactivates the gene. This inactivation process is called methylation. When the gene is inactivated, the cell may make little or none of the needed FMRP.
What goes wrong in a mutated gene?
A number of things can go wrong in a gene that can result in a mutation. The mutation affects the gene's ability to make the needed amount of protein or to make enough usable protein. Some of these mutations include:
In the case of Fragile X, usually the FMR1 gene is present, and its chemical sequence is correct, so neither A nor B apply. However, a mutated FMR1 gene includes repeats of a specific sequence in its promoter region, which creates a mutation like the one shown in situation C.
The number of repeats and their effects are still being studied. At the time this article was printed, the numbers included here were the most commonly cited for premutation in the published scientific literature: Fragile X Syndrome Handbook (2002) National Fragile X Foundation; American College of Medical Genetics Statement: Technical Standards and Guidelines for Fragile X (2001); Rousseau et al. (1996) American Journal of Human Genetics 59(Suppl):A188-1069. However, some research categorizes the premutation differently. For instance, in Crawford et al., 61 to 200 repeats is a premutation, while 41 to 60 repeats is an intermediate mutation (Genetics in Medicine 2001; 3:359-371). The American Academy of Pediatrics Policy Statement. Health Supervision for Children with Fragile X Syndrome uses 50 to 200 repeats for premutation (Pediatrics 1996; 98(2): 297-300). Tassone et al. (American Journal of Medical Genetics 2000; 97:195-203) use large premutation (100 to 200 repeats) and small premutation (55 to 100 repeats). You may encounter differences in the number of repeats for a premutation depending on your source.
One interesting aspect of Fragile X is that, even with a full mutation gene, the body may be able to make some FMRP. Three things affect how much FMRP is produced:
Medically Reviewed by a Doctor on 4/4/2014
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