Which are the causes of Fragile X Syndrome?

Fragile X Syndrome is a genetic disorder that affects the X chromosome, causing a range of developmental and intellectual disabilities. It is the most common inherited cause of intellectual disability and autism spectrum disorder.

The primary cause of Fragile X Syndrome is a mutation in the FMR1 gene, located on the X chromosome. This gene provides instructions for making a protein called fragile X mental retardation protein (FMRP), which is essential for normal brain development and function. In individuals with Fragile X Syndrome, there is a mutation in the FMR1 gene that leads to a deficiency or absence of FMRP.

The mutation responsible for Fragile X Syndrome is an expansion of a specific DNA sequence called CGG repeats within the FMR1 gene. Normally, this sequence is repeated between 5 and 44 times. However, in individuals with Fragile X Syndrome, the CGG repeats are expanded to over 200 times, resulting in a fragile site on the X chromosome. This fragile site is where the name "Fragile X" comes from.

The expansion of CGG repeats in the FMR1 gene leads to a variety of molecular and cellular changes that contribute to the symptoms of Fragile X Syndrome. One of the key effects is the silencing of the FMR1 gene, preventing the production of FMRP. Without sufficient FMRP, normal brain development and function are disrupted.

The inheritance pattern of Fragile X Syndrome is unique due to its association with the X chromosome. Since males have one X and one Y chromosome, a single copy of the mutated FMR1 gene is enough to cause the disorder. Therefore, Fragile X Syndrome is typically more severe in males. Females, on the other hand, have two X chromosomes, so they can have one normal FMR1 gene that compensates for the mutated gene. As a result, females may exhibit milder symptoms or be carriers of the disorder without showing any symptoms themselves.

It is important to note that the number of CGG repeats in the FMR1 gene can vary among individuals, leading to different levels of FMRP deficiency and varying degrees of symptom severity. Individuals with 55 to 200 CGG repeats are considered to have a premutation, which may not cause Fragile X Syndrome but can increase the risk of having children with the full mutation.

The exact mechanisms by which the absence of FMRP leads to the symptoms of Fragile X Syndrome are still being studied. However, researchers believe that FMRP plays a crucial role in regulating the production of other proteins involved in synaptic function and plasticity, which are essential for learning and memory. The deficiency of FMRP disrupts these processes, leading to the cognitive and behavioral impairments observed in individuals with Fragile X Syndrome.

In conclusion, Fragile X Syndrome is primarily caused by a mutation in the FMR1 gene, resulting in the absence or deficiency of the fragile X mental retardation protein (FMRP). This mutation involves an expansion of CGG repeats in the FMR1 gene, leading to a fragile site on the X chromosome. The inheritance pattern of Fragile X Syndrome is linked to the X chromosome, with males being more severely affected. Understanding the causes of Fragile X Syndrome is crucial for developing targeted therapies and interventions to improve the lives of individuals with this genetic disorder.