What is fragile X syndrome?
Fragile X syndrome is a genetic condition that is associated with a range of developmental problems. Affected individuals may have some degree of mental retardation or learning disabilities, delay in development of speech, anxiety, mood problems, attention deficit disorder (ADD) and features of autism spectrum disorders. They may also have characteristic physical features such as long and narrow face, large ears, high arched palate, flat feet, and overly flexible joints (especially fingers). Fragile X syndrome affects approximately 1 in 4,000 males and 1 in 8,000 females, with males usually more severely affected than females.
What is the cause of fragile X syndrome?
Fragile X syndrome is caused by the loss or deficiency in the fragile X mental retardation protein (FMRP), which is the product of FMR1. Affected individuals have more than 200 repeats of a CGG sequence in the 5’ UTR of the gene. This change is accompanied by abnormal modification of DNA in the neighboring gene promoter region, leading to silencing of the gene.
People with 55 – 200 CGG repeats are said to carry a premutation of FMR1. Most of these individuals are intellectually normal. However, some of them may have mild versions of the features seen in fragile X syndrome. Female premutation carriers have an increased risk of a disorder called fragile X-associated primary ovarian insufficiency (FXPOI), which can cause irregular menstrual cycles, early menopause and infertility. Male carriers have increased risk later in life (usually after age 50) of developing fragile X-associated tremor/ataxia syndrome (FXTAS), which results in movement and cognition problems.
How is fragile X syndrome inherited?
Male carriers pass on the premutation without expanding the CGG repeats. Since the FMR1 gene is on the X chromosome, they pass the premutation only to their daughters. In contrast, female carriers can have the premutation expand to a full mutation of more than 200 CGG repeats in cells that develop into eggs. Therefore these women have an increased risk of having a child with fragile X syndrome.
What is this series of tests for?
The fragile X carrier screening (FMR1 Repeats Analysis) test (test codes: GFS) detects the expansion of tri-nucleotide (CGG) repeats in the 5’ untranslated region (5’ UTR) of the fragile X mental retardation 1 (FMR1) gene on the X chromosome. The fragile X FMR1 methylation analysis (test code: GFX) detects expansion of tri-nucleotide (CGG) repeats in the 5’ UTR, as well as the methylation status at the neighboring CpG island of the FMR1 gene.
Who should consider this test?
- Individuals with autism, developmental delay or mental retardation
- Individuals with any physical or behavioral characteristic of Fragile X syndrome or family history of Fragile X syndrome
- Individuals having intermediate allelic form (gray zone) for identification of the risk of expansion in future generations and stability of the allele transmission
- Fetuses of known carrier mother
- Affected individuals or relatives in the context of a positive cytogenetic Fragile X test result
Test Specifications
Rejection criteria
- Specimen without proper labeling
- Specimen not in requested format or insufficient quantity
- Specimen in container expired for more than 1 month
- Container leakage
- Sampling date is more than 7 days
- Frozen specimen, specimen (except blood) grossly contaminated with red cells
Factor(s) known to affect results
- Improper collection, handling and storage of specimen