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HelpTest Code LAB1847 Fragile X DNA
Clinical System Name
Fragile X DNA Analysis Request
Synonyms
FMR1
FRAX A
Description
Molecular (DNA) testing to determine the number of CGG repeats in the FMR1 gene.
The test is indicated for:
1. Evaluation of male and female patients with an intellectual disability, developmental delay and autism.
2. Evaluation of women with premature ovarian failure.
3. Evaluation of older adult males with gait ataxia or intention tremor.
4. Carrier testing for women in a family with history of fragile X syndrome or undiagnosed intellectual disability.
Sample Requirements
Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood collection if the patient received leuko-reduced red cells or plasma.
Specimen: Whole blood, cord blood
Container(s): Lavender/EDTA, Yellow/ACD A or B
Preferred Vol: 3 mL
Minimum Vol: 1 mL
Specimen: Extracted DNA from EDTA blood
Minimum: 5µg
Note: Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
laboratory or a laboratory meeting equivalent requirements as determined by the CAP
and/or the CMS. DNA concentration minimum 100 µg/mL; 260/280 ratio 1.70-2.00
Processing Instructions
Reject due to: n/a
Spin: No
Aliquot: No
Temp: Refrigerate
Storage location: Molecular Genetics box in CPA refrigerator #2 - for both extracted DNA and blood
Off-site collection: Transport all sample types at room temperature via overnight shipping.
Stability
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood, extracted DNA | Room temp | 3-5 days for blood |
| Whole blood, extracted DNA | Refrigerated | 7 days for blood |
| Extracted DNA | Frozen | ok |
Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.
Availability
| STAT | Performed | TAT |
|---|---|---|
| Contact lab | Monday - Friday | 2-3 weeks |
Performing Laboratory
Seattle Children's Laboratory
Department
Department: Molecular Genetics Laboratory
Phone: 206-987-3872
Lab Client Services: 206-987-2617
Lab Genetic Counselor: LabGC@seattlechildrens.org
CPT Codes
81243 (updated 11/2/16 by jnaray)
Methodology
Method: PCR
Reference Range
Interpretive report will be provided
Special Instructions
Links to: FMR1-Related Disorders- GeneReviews
Requisition
Clinical Utility
FMR1-related disorders include fragile X syndrome, FMR1-related premature ovarian failure (POF), and fragile X-associated tremor/ataxia syndrome (FXTAS). These disorders are due to a repetitive sequence of DNA (CGG repeat) that leads to an expansion of the FMR1 gene. A normal FMR1 gene has approximately 5-44 CGG repeats. Approximately 55-200 repeats are considered premutations and >200 CGG repeats is a full mutation and causes fragile X syndrome. An estimated 1 in 4000 males are affected with fragile X syndrome. Features include developmental delay, learning disabilities, attention deficit, speech delay, gross and fine motor delay, and autistic like behavior. Many females are unaffected carriers of the full expansion, however, females can exhibit symptoms as well. Female carriers of a premutation can have FMR1-related premature ovarian failure. Male premutation carriers can develop FXTAS, characterized by white matter lesions on MRI causing intention tremor or gait ataxia.
More than 99% of individuals with Fragile X syndrome have a loss-of-function variant of FMR1 caused by an increased number of CGG trinucleotide repeats (typically a full mutation, >200 repeats) accompanied by aberrant methylation of FMR1 (FMR1-Related Disorders - GeneReviews). The clinical utility of reporting the estimated number of CGG repeats for a full expansion mutation has not been demonstrated for individuals expressing symptoms of Fragile X syndrome. In addition, the data suggest that the vast majority of FMR1 alleles >200 repeats are fully methylated. Methylation studies may be sent out upon provider request if the result does not fit the patient's phenotype.
As of 11/1/16, Fragile X E (FMR2) repeat analysis is no longer available at our laboratory. The SCH Laboratory Test Utilization Management Team has determined that this test has demonstrated a very low yield in the absence of family history of an FMR2 repeat expansion and there is no evidence-based clinical utility for this test.