Variation in the number of CGG repeats in the FMR1 gene at the bottom of the X chromosome can lead to increased levels of mRNA or decreased levels of protein—both conditions that cause disease.
Randi Hagerman
Sep 1, 2019
Fragile X syndrome is caused by an expansion of CGG nucleotide repeats in the FMR1 gene at the end of the long arms of the X chromosome. To identify the mutation, researchers culture cells in media deficient in folic acid, which causes the ends of the X chromosome to appear as though they are about to break off. Before molecular testing, this was the only way to see the mutation.
The FMR1 gene encodes the fragile X mental retardation protein (FMRP), which regulates gene expression and protein translation in the brain. FMRP is important for maintaining synaptic plasticity and the ability to make new neurons. Levels of FMRP associated with disease severity in patients with FXS.
The Fragile X Mutation![]() the scientist staff Fragile X syndrome is caused by an expansion of CGG nucleotide repeats in the FMR1 gene at the end of the long arms of the X chromosome. To identify the mutation, researchers culture cells in media deficient in folic acid, which causes the ends of the X chromosome to appear as though they are about to break off. Before molecular testing, this was the only way to see the mutation. The FMR1 gene encodes the fragile X mental retardation protein (FMRP), which regulates gene expression and protein translation in the brain. FMRP is important for maintaining synaptic plasticity and the ability to make new neurons. Levels of FMRP associated with disease severity in patients with FXS.
InheritanceIn males: Full mutations revert back to premutations during development of X chromosome–carrying sperm. Thus, men with the full mutation or the premutation pass the premutation on to their daughters. Because it is X-linked, they cannot pass it on to their sons. In females: Premutations of 100 CGG repeats or more convert to the full mutation during egg development or in the embryo. Thus, women with the full mutation or a premutation with 100 repeats or more on one of their X chromosomes pass on the full mutation to their children approximately 50 percent of the time. Women with a premutation of fewer than 100 repeats will pass on a full mutation less often. ![]() ![]() ![]() ![]() Occasionally, if both parents carry premutations or full mutations, their daughters can inherit two fragile X chromosomes: one with a premutation from the father and the other with either a premutation or a full mutation from the mother. THE SCIENTIST STAFF |
Randi Hagerman is a Distinguished Professor of Pediatrics at the MIND Institute and Department of Pediatrics, University of California, Davis, Medical Center, Sacramento.
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