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Thread: The Fragile X

  1. #1
    Join Date
    Oct 2005
    Portland, Oregon USA

    Red face The Fragile X

    Just a post to help bring awareness to the Fragile X Syndrome:

    find more information here:

    Summary of Fragile X Syndrome
    What Causes Fragile X Syndrome? A short animation from the Centers for Disease Control - National Center on Birth Defects & Developmental Disabilities
    Prevalence of fragile X syndrome
    Fragile X syndrome is the most common inherited cause of mental impairment. The syndrome occurs in approximately 1 in 3600 males and 1 in 4000 to 6000 females.
    Impact on males
    The majority of males with fragile X syndrome will have a significant intellectual disability. The spectrum ranges from learning disabilities to severe mental retardation and autism.
    In addition, males have a variety of physical and behavioral characteristics. However, no male has all of these characteristics.
    Physical features such as enlarged ears, long face with prominent chin, and large testicles (in post pubertal males) are common. Connective tissue problems may include ear infections, mitral valve prolapse, flat feet, double-jointed fingers, hyperflexible joints and a variety of skeletal problems.
    Behavioral characteristics in males include attention deficit disorders, speech disturbances, hand biting, hand flapping, autistic behaviors, poor eye contact, and unusual responses to various touch, auditory or visual stimuli.
    Impact on females
    The characteristics seen in males can also be seen in females, though females often have milder intellectual disability and a milder presentation of the behavioral or physical features.

    About a third of the females have a significant intellectual disability. Others may have more moderate or mild learning difficulties. Similarly, the physical and behavioral characteristics are often expressed to a lesser degree.
    A change or mutation in a gene on the X chromosome causes the fragile X syndrome. Chromosomes are packages of genes that are passed from generation to generation. Most individuals have 46 chromosomes, two of which are sex chromosomes. In females, these are two X's; in males they are and X and Y. Genes are given names to identify them and the gene responsible for fragile X syndrome is called the FMR1 (fragile X mental retardation 1) gene. The mutation is in the DNA (the chemical that makes up genes), of the X chromosome. The gene appears in three forms that are defined by the number of repeats of a pattern of DNA called CGG repeats. Individuals with less than 60 CGG repeats have a normal gene. Individuals with 60-200 CGG repeats have a premutation which means they carry an unstable mutation which can expand in future generations. Individuals with over 200 repeats have a full mutation which causes fragile X syndrome. The full mutation causes the gene to shut down or methylate a region of the FMR-1 gene. Normally, the FMR-1 gene produces an important protein called FMRP. When the gene is turned off, the individual does not make fragile X mental retardation protein (FMRP). The lack of this specific protein causes fragile X syndrome.
    At this time, there is no cure for fragile X syndrome. However, special education, speech and language therapy, occupational therapy and behavioral therapies are helpful in addressing many of the behavioral, and cognitive issues in fragile X syndrome. In addition, medical intervention including medications can be helpful for aggression, anxiety, hyperactivity and poor attention span. Because the impact of fragile X is so varied, it is important to do a careful evaluation of the individuals' abilities and difficulties to tailor a treatment plan to address specific needs.
    During the 1970's and 1980's the test available for diagnosing fragile X syndrome was the chromosomal or cytogenetic test. While it was helpful, it was not always accurate. In the 1990's, two molecular DNA tests became available. These are:
    The Southern Blot analysis -this determines if the gene has a full mutation and its approximate size, if the gene has been methylated and if there is mosaicism (a mixture of different cell types).
    The polymerase chain reaction (PCR) analysis can determine the actual number of repeats in individuals with a normal size gene or with a premutation. It is not the test of choice to diagnose a full mutation, but is quite accurate in determining premutation and normal gene repeat numbers.
    Fragile X syndrome is one of a group of conditions called trinucleotide repeat disorders. A common feature of these conditions is that the gene can change sizes over generations, becoming more unstable, and thus the conditions may occur more frequently or severely in subsequent generations. These conditions are often caused by a gene change that begins with a premutation and then expands to a full mutation in subsequent generations.

    Premutations are defined as having 60-200 CGG repeats and can occur in both males and females. In males it usually does not expand to a full mutation when passed on to his daughters (A male carrier never passes on the fragile X gene to his sons as he passes on his Y chromosome to his son. A female with the premutation will often pass on a larger version of the mutation to her children. As the size of the premutation increases, there is an increased possibility that a child will receive the full mutation. Typically, the premutation has no observable impact. However, some females with a premutation will experience early menopause. (POF) Additionally, some older adults with premutations may develop a neurological condition called FXTAS (often misdiagnosed as a "Parkinson's-like" condition). Approximately 1 in 250 females and 1 in 800 males carry the premutation.
    Full mutation

    A full mutation is defined as having over 200 CGG repeats on the southern blot DNA test. In addition, most full mutation genes have some degree of methylation (the process which "turns off" the gene). Males with a full mutation usually have fragile X syndrome, though there is a small percentage of males with a full mutation who do not have mental retardation. About 30% of females with a full mutation have no cognitive deficits. The remaining 65-70% of females with a full mutation will have some difficulties with cognitive, behavioral, or social functioning and may have some of the physical features found in males.

    Fragile X in an "X-linked" condition, which means that the gene is on the X chromosome. Since a woman has two X chromosomes a woman with a premutation or full mutation has a 50% chance of passing on the X with the mutation in each pregnancy. If she has a premutation, and it is passed on (to either males or females), it can remain a premutation or it can expand to a full mutation. If she has a full mutation and it is passed on (to either males or females), it will remain a full mutation. In many X linked conditions only males who inherit the abnormal gene are affected, however in fragile X syndrome females can also be affected. Additionally, in other X linked conditions all males who carry the gene are affected, however in fragile X syndrome, unaffected males can carry the gene in the premutation form and have no symptoms of fragile X syndrome. Males with the premutation will pass it on to all of their daughters and none of their sons (they pass their Y chromosome on to their sons).
    History of fragile X syndrome
    In 1943, Martin and Bell showed that a particular form of mental retardation (later known as fragile X syndrome) was X-linked. In 1969, Herbert Lubs developed the chromosomal test for Fragile X. The test was not used extensively until the late 1970's. In 1991 the FMR1 gene that causes Fragile X was identified.

    For a more detailed analysis of fragile X syndrome, begin with one of the following questions.
    What are the physical & psychological characteristics of fragile X syndrome?
    How can you test to see if someone has fragile X syndrome?
    What interventions address the problems related to fragile X syndrome?
    What causes fragile X syndrome?
    Educational issues related to fragile X syndrome.
    How can you plan for the legal and financial issues raised by fragile X syndrome?
    For a review of molecular studies, see:
    O'Donnell, WT, Warren ST. 2002. A decade of molecular studies of fragile X syndrome. Annu. Rev. Neurosci 25:315-38
    Liane J .Abrams, M.S.
    Certifed Genetic Counselor
    National Fragile X Foundation

  2. #2
    Join Date
    Feb 2007
    Montreal, Canada

    Re: The Fragile X

    Having been involved in FMRP research a while ago, I can only support RAV TUX initiative.


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