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Fragile X with Reflex to Methylation Analysis (8000101297)
Test Mnemonic:


Specimen Requirements:

Whole Blood


Lavender (EDTA), pink (K2EDTA), blue (Na Citrate) or yellow (Acid Citrate Dextrose) collection tube.

Minimum Volume:





30 days

Causes for Rejection:

Incorrect tube, inadequate volume

Reference Range:
Turnaround Time:

4-10 days


Polymerase Chain Reaction / Fragment Analysis


Molecular Diagnostics Laboratory


FMR1, Fragile X Mental Retardation 1, Fragile X

CPT 4 Code:

81243, 81244 added if reflexed


Phenotype Characteristics: Fragile X syndrome is one of the most common causes of inherited mental retardation, intellectual disability, and autism. The vast majority of cases are caused by expansion of a CGG repeat and abnormal methylation in the fragile X mental retardation 1 gene (FMR1). Expanded FMR1 CGG repeats that range in size from 55 to 200 repeats (ie, premutations) can cause fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI).

Prevalence: Fragile X syndrome occurs in approximately 1 in 3,600 males and 1 in 4,000-6,000 females. Approximately 1 in 250 females and 1 in 500 males carry FMR1 premutation.

Inheritance: X-linked dominant.

Penetrance: Reduced in females.

Cause: Expansion of FMR1 CGG triplet repeat.

Full mutation: >200 CGG repeats (methylated)
Premutation:   55-200 CGG repeats (unmethylated)
Intermediate:   45-54 CGG repeats (unmethylated)
Normal:           5-44 CGG repeats (unmethylated)

Clinical Sensitivity: 99 percent.

Methodology: Triplet repeat–primed polymerase chain reaction (TRP PCR) followed by size analysis using capillary electrophoresis. Methylation-specific PCR analysis is performed for CGG repeat of 55 or greater. Methylation analysis is used to distinguish between premutation and full mutation alleles. This test was developed and its performance characteristics were determined by UTMB Pathology Molecular Diagnostics Laboratory. It has not been cleared or approved by the U.S. Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory testing.

Analytic Sensitivity and Specificity: 99 percent.

Limitations: Diagnostic errors can occur due to rare sequence variations. FMR1 mutations, other than those targeted, will not be detected.

Counseling and informed consent are recommended for genetic testing.


Online Mendelian Inheritance in Man (OMIM) numbers: 309550 (FMR1), 300624 (fragile X syndrome), 300623 (FXTAS), and 311360 (FXPOI).

Online GeneReviews profile for FMR1-related disorders:

When ordering tests for which Medicare or Medicaid reimbursement will be sought, physicians should only order tests that are medically necessary for the diagnosis or treatment of the patient. Components of the organ or disease panels may be ordered individually. The diagnostic information must substantiate all tests ordered and must be in the form of an ICD-10 code or its verbal equivalent.
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