Preferred test to diagnose fragile X syndrome and carrier screening in individuals with a positive family history.
Polymerase Chain Reaction/Capillary Electrophoresis
Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 5 mL whole blood. (Min: 1.5 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background Information for Fragile X (FMR1) with Reflex to Methylation Analysis
Characteristics of Fragile X syndrome (FXS): Affected males have moderate intellectual disability, hyperactivity, perseverative speech, social anxiety, poor eye contact, hand flapping or biting, autism spectrum disorders and connective tissue anomalies in males. Females are usually less severely affected than males. FXS is caused by FMR1 full mutations.
Characteristics of Fragile X Tremor Ataxia Syndrome (FXTAS): Onset of progressive ataxia and intention tremor typically after the fourth decade of life. Females also have a 21 percent risk for primary ovarian insufficiency. FXTAS is caused by FMR1 premutations.
Incidence of FXS: 1 in 4,000 Caucasian males and 1 in 8,000 Caucasian females.
Penetrance of FXS: Complete in males; 50 percent in females.
Penetrance of FXTAS: 47 percent in males and 17 percent in females >50 years of age.
Cause: Expansion of the FMR1 gene CGG triplet repeat.
Full mutation: typically >200 CGG repeats (methylated).
Premutation: 55 to approx 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 (PCR) followed by size analysis using capillary electrophoresis. Methylation-specific PCR analysis is performed for CGG repeat lengths of >100 to distinguish between premutation and full mutation alleles.
Analytic Sensitivity and Specificity: 99 percent; estimated precision of sizing for intermediate and premutation alleles is within 2-3 CGG repeats.
Limitations: Diagnostic errors can occur due to rare sequence variations. Rare FMR1 variants unrelated to trinucleotide expansion will not be detected. A specific CGG repeat size estimate is not provided for full mutation alleles. AGG trinucleotide interruptions within the FMR1 CGG repeat tract are not assessed.
|Phenotype||Number of CGG Repeats|
Laboratory Developed Test (LDT)
If a CGG repeat of 100 or greater is detected by PCR and Capillary Electrophoresis, methylation analysis will be added. Additional charges apply.
81243; if reflexed, add 81244
|Component Test Code*||Component Chart Name||LOINC|
|0050556||Fragile X Allele 1||45321-7|
|0050558||Fragile X Allele 2||45322-5|
|0050559||Fragile X Methylation Pattern||41107-4|
|0050579||Fragile X Interpretation||36913-2|
|2001310||FRAG X Specimen||66746-9|
- Inherited Mental Retardation (Fragile X (FMR1) Diagnostic)
- Martin-Bell Syndrome (Fragile X (FMR1) Diagnostic)