• Test Code:
    1480
  • Department:
  • Test Synonyms:
    FMR1-Related Disorders Frax A Mental Retardation
  • CPT Code(s):
    8124381244 (if expansion is found)
Background:

Fragile X syndrome is the most common form of inherited intellectual and developmental disabilities (IDDs).  Fragile X syndrome is the result of an expansion of a trinucleotide repeat (CGG) in the Fragile X Mental Retardation 1 (FMR1) gene located on the X chromosome.  Full size repeat expansions result  in methylation of the FMR1 gene and the lack of a gene product.  Fragile X is inherited as an X-linked disorder and affects both males and females. All mothers of males affected with fragile X syndrome are premutation carriers, and all full mutations arise from premutations.  Premutation carriers may be affected with Fragile X-associated Tremor Ataxia Syndrome (FXTAS), which is generally found in older premutation male carriers and consists of tremor and ataxia.  Premutation female carriers may be affected with FMR1-associated primary ovarian insufficiency (POI), and occasionally with tremor and ataxia.  Genetic counseling is recommended for all premutation and full mutation carriers.

Reason for Referral

Testing is indicated for mentally retarded individuals and for individuals with a family history of mental retardation or learning disability of unknown etiology.

Methodology:

PCR and capillary electrophoresis  analysis is used to measure the number of CGG trinucleotide repeats in the 5’ untranslated region of the FMR1 gene at Xq27.3; additionally, CGG repeat size and methylation status is determined by Southern blot for large premutations (>CGG150) and for fully expanded alleles.

Allele Types #CGG Repeats:
       Normal: 5 - 44
       Intermediate: 45 - 54
       Premutation: 55 – 200
       Full mutation (i.e. disease-causing): >200

Specimen Requirements:

Blood: EDTA (purple-top) tube or ACD (yellow-top) tube

    • Adult: 6mL
    • Child: 3mL

DNA: 20ng at a minimum of 100ng/µL

Prenatal testing:

  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amnio or CVS (2-T25 flasks)
  • When testing CVS, sizing can be performed and expansions will be detected but methylation status may not be reliably determined.If methylation status is requested or required by the referring provider, testing of CVS is not recommended.

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received.Please provide maternal blood in addition to the fetal specimen.Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Direct Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories.Cell cultures will be prepared from the specimen received.Additional charges apply for confirmatory testing.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

7-10 days. If expansion found, add 14 days to turn around time.

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold. but not frozen.
  • Contact Client Services for shipping kits and instructions. 
  • Please use the cold pack provided in the KDL shipping kit. 
  • Ship the specimen overnight express, using the FedEx priority overnight label provided. 

References:

  1. NCBI GeneReviews: FMR1-Related Disorders by Robert A. Saul and Jack C. Tarleton (2012) http://www.ncbi.nlm.nih.gov/books/NBK1384/
  2. Monaghan et al. 2013 Genet Med 15(7)

Additional Info:

Related testing in laboratory:
    Fragile X-associated Tremor Ataxia syndrome (FXTAS) and
    FMR1-associated Primary Ovarian Insufficiency (POI).
 
Prior to any genetic testing we recommend genetic counseling. To receive forms and information about prenatal diagnostic testing, please contact Client Services at (855) 535-1522. 

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