Fragile X Syndrome: FMR1 Trinucleotide Repeat Analysis

Turnaround Time

7-10 days for samples with 45 repeats

CPT Code(s)

81243

Cost

$350

Genes

• Fragile X syndrome

Fragile X Syndrome is the most common form of inherited intellectual disability. Approximately 1/1250 males and 1/2500 females are affected by the condition. Some population studies have shown the carrier frequency to be as high as 1/250 individuals. The American College of Medical Genetics policy statement on Fragile X testing recommends consideration of testing for males or females with intellectual disability, developmental delay or autism, those with a family history of Fragile X syndrome or unexplained intellectual disability. Additionally, prenatal testing should be offered to known carrier females. Trinucleotide repeat analysis is the standard for Fragile X diagnosis. Patients with the above characteristics who had a previously normal cytogenetic Fragile X results should also be considered for trinucleotide repeat analysis.

Trinucleotide Repeat

More than 99% of cases are due to the expansion of a polymorphic (CGG) repeat within the FMR1 gene. Fragile X testing at the Greenwood Genetic Center involves two independent molecular approaches. PCR analysis is performed initially to determine allele sizes. Samples with allele sizes of less than 55 repeats are reported out in approximately 7-10 days. If an allele size of 55 repeats or greater is detected, the sample will be reflexed to methylation-sensitive PCR to confirm the presence of an expansion and determine methylation status. Patients positive for a full mutation will be reported as having greater than 200 CGG repeats.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.