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DNA Analysis:
Fragile X Syndrome (FRAXA)
Fragile X syndrome is the most common cause of inherited mental retardation with an incidence of approximately 1 in 1,500 males and 1 in 2,000 females. Affected males typically display mental retardation with characteristic physical features. Females are usually less severely affected than males. Approximately 30% of females exhibit mild mental retardation. Fragile X syndrome is an X-linked disorder caused by an expansion of an unstable CGG trinucleotide repeat in the fragile X gene (FMR-1). This trinucleotide repeat is variable in length. Normal individuals have from 5 to 44 repeats. Unaffected carriers of a fragile X mutation have what is termed a premutation. These individuals have from 55 to 200 trinucleotide repeats. In patients with fragile X syndrome, the premutation has expanded to greater than 200 repeats. Expansions in this range are termed full mutations and result in complete disruption of the FMR-1 gene. A gray zone repeat range exists from 45 to 54 repeats. Repeat numbers in this range have been shown to be stable in some families and unstable in others. Probabilities of expansion are available for families with repeat numbers in the premutation repeat range.
CGG repeat ranges are based on recommendations from the American College of Medical Genetics/Technical Standards and Guidelines for Fragile X.
- Individuals with mental retardation, developmental delay, or autism
- Individuals with a family history of fragile X syndrome
- Individuals with a family history of undiagnosed mental retardation
- Individuals with a cytogenetic test result for fragile X that is discordant with their phenotype
- Prenatal diagnosis for documented fragile X carrier females
- Carrier status must be documented in the mother prior to prenatal studies.
Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a progressive neurodegenerative disorder primarily affecting fragile X premutation carrier males over age 50. The penetrance of FXTAS increases with age.
Females with premutations are at increased risk for premature ovarian failure or ovarian dysfunction.
Direct mutation analysis: Our testing methodology incorporates polymerase chain reaction (PCR) and Southern blot technologies. Fluorescent labeled primers are used to amplify the CGG repeat region in the FMR1 gene. PCR is followed by capillary electrophoresis on the ABI 3130 Genetic Analyzer. PCR analysis is useful in determining repeat numbers in the normal and premutation ranges. Southern analysis with the probe pE5.1 detects full expansions of the CGG trinucleotide repeat.
In greater than 99% of cases, fragile X syndrome is caused by an expansion of the unstable CGG trinucleotide repeat in the FMR-1 gene. This assay will not detect the small number of remaining cases caused by other mechanisms such as deletion or point mutation. This assay will also not detect cases of another mental retardation syndrome associated with the FRAXE locus.
Blood: For adults, 5 cc collected in a purple top (EDTA) or yellow top (acid citrate dextrose) vacutainer tube. For children, 1 - 2 cc is sufficient. Do not centrifuge or freeze. Sample may be refrigerated or stored at room temperature.
Please contact the laboratory at 858-534-3093 for information on prenatal testing.
A blood sample from the mother is required for prenatal testing to rule out maternal cell contamination.
14 days
PCR: 83890, 83894, 83900, 83901, 83909 (2X), 83912
For PCR and Southern blot add 83892, 83896, 83897
For prenatal studies add 88235
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