Many of us across the country have been waiting for summer to finally show up. We celebrate the 4th of July with fireworks and festivals to raise awareness of our freedom and the welcome summer. Did you know that July is fragile X month, with July 22Nd called Fragile X Awareness Day?1 Fragile X is the main cause of inherited intellectual disability. It can also be associated with other health problems in men and women who carry a fragile X mutation but have normal intelligence.

Image courtesy of FragileX.org (https://fragilex.org)

Fragile X syndrome is more common in boys, but girls may also inherit the condition

Fragile X syndrome got its name from the test result, which was first used to diagnose it. When the blood of affected individuals was exposed to certain conditions and then analyzed for chromosomes, part of their X chromosome looked as if it would depend, broken or “fragile”.

Fragilex is caused by a modified gene on the X chromosome, FMR1. Most girls have two X chromosomes and most boys have an X and y chromosomes. Fragile X syndrome is an X-linked disease because the gene is located on the X chromosome. Fragile X syndrome is usually passed on by a carrier or affected mother to her child. Because boys have only one X chromosome, they tend to have more severe symptoms when they inherit the altered gene, compared to girls who have two X chromosomes.  However, unlike many X-linked conditions, girls may also be affected if they inherit this altered gene.

Fragilex is caused by a triplet repeat mutation in the FMR1 gene

The underlying genetic cause of Fragile X was discovered in 1991.2.3.4 The type of DNA change in the gene is called extended triplet repetition. This triplet repeat can be present in different sizes and explains the variety of symptoms we can see in people who carry a mutation. Now that DNA modification is understood, tests for Fragile X are performed by DNA analysis rather than chromosome analysis.

There are three separate conditions caused by a modified FMR1 gene

  • Fragile X Syndrome (FXS): Boys and rare girls are affected by a number of intellectual disabilities and behavioural problems, including autistic behavior, attention deficit disorder and attention deficit hyperactivity disorder, as well as some characteristic physical characteristics that would be recognized by a doctor.
  • Fragile X-associated tremor ataxia syndrome (FXTAS): These are symptoms of uncontrolled tremors, balance disorders and memory problems. They occur in otherwise unaffected persons, usually after the age of 50.
  • Fragile X-Associated Primary Ovarian insuffficiency (FXPOI): This refers to a number of ovarian function problems, including infertility and early menopause in otherwise unaffected women under the age of 40.

What is the risk of being a carrier?

Since Fragile X syndrome is inherited, there may be traits in a family that indicate whether there is a risk of carrying this altered gene. If someone is pregnant or planning to become pregnant, they may want to know if the risk for a child with fragile X syndrome is increased. Do they have relatives with intellectual disabilities, autism spectrum disorders or other behavioral disorders? Are there female relatives with early or premature menopause? Are there relatives with later the neurological findings of tremors, memory loss or personality or psychiatric changes? If so, there may be an increased risk and carrier screening for Fragile X is an option to get more information.

For more information about Fragile X, FXTAS, and FXPOI, visit the website: www.fragilex.org.

Information about research on the treatment or cure of Fragile X: www.fraxa.org.5th

References
1. National Fragile X Foundation website https://fragilex.org.
2. Oberle I, et al. Instability of a 550-base pair of DNA segment and abnormal methylation in fragile X syndrome. Science. 1991;252:1097-1102.
3. Verkerk AJMH, et al. Identification of a gene (FMR-1) containing a CGG repeat that is coincident with a breakpoint cluster area with length variations in fragile X syndrome. Cell,1991;65:905-914.
4. Yu S, et al. Fragile X genotype characterized by an unstable DNA region. Science, 1991;252:1179-1181.
5. FRAXA Research Foundation. fraxa.org.



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