Diagnostic Test Directory

Molecular Genetics Laboratory

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Fragile X Syndrome (FMR1)

  • Synonyms: Martin-Bell Syndrome
  • LIS Mnemonic: MBFRAX


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 1 ug extracted DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


2-6 weeks



Disease Information

Clinical Features:

Fragile X is an X-linked disorder and the most common cause of inherited mental retardation, affecting one male in 1,500 and one female in 2,500. It is characterized by mild to severe MR and is often associated with some facial dysmorphism, joint laxity, and large testes in postpubertal males. Behavioral abnormalities, including autism spectrum disorder, are common. The fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in males who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor. FMR1-related premature ovarian failure (POF) occurs in approximately 20% of females who have an FMR1 premutation.

Molecular Genetics:

The FMR1 gene is located on chromosome Xq27.3. The inheritance pattern is X-linked. The fragile X mutation involves the expansion of a CGG repeat sequence located in the 5’ flanking region of the FMR1 gene. The different classes of alleles are: 1) Normal alleles (5-40 repeats): Alleles of this size are stably transmitted without any increase or decrease in repeat number. 2) Intermediate or gray zone alleles (41-58 repeats): The frequency and magnitude of repeat instability increases with alleles containing more than 50 repeats. An important predictor of repeat instability in large intermediate alleles (>50 repeats) is the number of "pure" CGG repeats without interrupting AGG repeats. Increasingly longer pure repeats, especially those with more than 35 uninterrupted CGG repeats, are more likely to become unstable. 3) Premutation alleles (59-200): Alleles of this size are unmethylated and are not associated with mental retardation but do convey increased risk for FXTAS and POF. Because of potential repeat instability upon transmission of premutation alleles, women with alleles in this range are considered to be at risk of having children affected with fragile X syndrome. 4) Full mutation alleles (>200 repeats). Alleles of this size are methylated which results in loss of expression of the gene (present in only one copy in males) and phenotypic expression of the disease.

Test Methods:

The promoter region of the FMR1 gene is amplified using the CGG Repeat Primer PCR kit (Asuragen Inc). Amplicons are resolved by capillary electrophoresis (ABI 3730) and sized using the ROX 1000 ladder. CGG repeats are calculated by comparing the size to FMR1 standards or directly quantified by counting the number of distinct CGG peaks using Gene Mapper. The accuracy of sizing of alleles in the normal, intermediate, and premutation range by this method is +/- 1 CGG repeat.

Detection Rate:

There is a greater than 99% detection rate for all cases of fragile X syndrome caused by the CGG expansion. Point mutations and deletions in the FMR1 gene will not be detected by this assay. NB: Sizing of intermediate alleles is not accurate by Southern Blot analysis.


Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.


To confirm a clinical diagnosis of fragile X syndrome, identify mutation carriers (including premutation, mosaic, and full mutation carriers), determine recurrence risk in families, determine predisposition to FXTAS or premature ovarian failure, and facilitate prenatal diagnosis of fragile X mental retardation.

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