Fragile X DNA Analysis (Fragile X FMR1 Repeat Analysis)
Fragile X Syndrome, the most common form of inherited mental retardation, is a genetic condition that leads to a wide range of developmental problems including learning disabilities and cognitive impairment.
PrintFragile X Syndrome, the most common form of inherited mental retardation, is a genetic condition that leads to a wide range of developmental problems including learning disabilities and cognitive impairment.
Mutations within the FMR1 gene have been associated with Fragile X syndrome, specifically involving the expansion of an unstable CGG trinucleotide repeat sequence. Females who are known to be premutation carriers are at increased risk of having premature ovarian failure (POF) and for repeat expansion to a full mutation in the next generation. Individuals with a premutation are also at increased risk later in life for Fragile X-associated tremor/ataxia syndrome (FXTAS).
The Ambry Test: Fragile X DNA Analysis includes FMR1 CGG repeat detection by PCR, and if a full mutation allele is detected, reflex to Southern blot for expansion confirmation and promoter methylation analysis. Greater than 99% of the mutations in FMR1 responsible for Fragile X syndrome are due to CGG repeat expansions.
Fragile X syndrome, the most common form of inherited mental retardation, is a genetic condition that leads to a wide range of developmental problems including learning disabilities and cognitive impairment.2 Mutations within the FMR1 gene have been associated with Fragile X syndrome, specifically involving the expansion of an unstable CGG trinucleotide repeat sequence in the 5’UTR region.3 While the general population may carry 6-50 CGG repeats, individuals affected with fragile X syndrome have >200 methylated repeats which leads to a silencing effect of the gene. 4,5 Individuals carrying between 50 and 200 repeats are said to be premutation carriers, and may exhibit social, emotional and cognitive issues along the fragile X spectrum as well as autism spectrum disorder.6 Females who are known to be premutation carriers are at increased risk of having premature ovarian failure (POF)7 and for repeat expansion to a full mutation in the next generation.8 Individuals with a premutation are also at increased risk later in life for Fragile X-associated tremor/ataxia syndrome (FXTAS).
Fragile X syndrome testing should be considered for any individual with mental retardation, developmental delay, learning disabilities of unknown cause, autism or autism-like characteristics. Testing should also be considered for families with a history of Fragile X syndrome or mental retardation due to unknown cause.
Prenatal testing is recommended for fetuses of mothers known to be Fragile X carriers, as well as for those with a family history of Fragile X syndrome or mental retardation of unknown cause.
If FMR1 promoter CGG repeat detection is requested, a triple primed polymerase chain reaction (PCR) using a standardized kit is used to selectively amplify the regions of gDNA corresponding to the FMR1 promoter gene followed by capillary electrophoresis for fragment size analysis. Southern blot confirmation of FMR1 expansions and methylation status is performed as a reflex test if PCR indicates a full mutation allele. Southern blot analysis is performed by UCLA Diagnostic Molecular Pathology Laboratory (11633 San Vicente Blvd., Los Angeles, CA 90049).
CGG repeat expansion in the FMR1 gene have been associated with >99% of clinically affected Fragile X syndrome patients. A small portion (<1%) of Fragile X cases are due to rare mutations in areas of the FMR1 gene not evaluated by this test.
Blood: Collect 5 ml minimum, 8-10 ml preferred, in an EDTA purple/lavender-top tube. Store at room temperature or refrigerate. Ship at room temperature. Specimen must be less than 5 days old upon receipt.
DNA: Minimum sample amount required at 2.1 mL at 100 nanogram concentration. Extraction protocol required.
Prenatal: Please call an Ambry Genetic Counselor to discuss your case
| Test Code | Technique | CPT Codes |
|---|---|---|
| 4544 | Fragile X DNA Analysis (FMR1) | 83891x1, 83894x1, 83900x1, 83901x21, 83909x1, 83912x1 |
| Technique | Days |
|---|---|
| Fragile X DNA Analysis (FMR1) | 7-14 |
1 Nol in, S et al. Am J Hum Genet 2003;72:454-464
2 Verkerk A. et al. Cell 1991;65:905-914
3 Rife M et al. Mol Hum Repro. 2004;10(10):773-776
4 Fu YH et al. Cell 1991;67:1047-1058
5 Hagerman P, Hagerman R Am J Hum Genet. 2004;74:805-816
6 Hessl D et al. Brain 2007;130:404-416
7 Pieretti M et al. Cell 1991;66:817-822
8 Grigsby, J et al. J of Neurol Sci 2006;248: 227-233