Preferred test to diagnose fragile X syndrome and carrier screening in individuals with a positive family history.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 5 mL whole blood. (Min: 1.5 mL)
- Storage/Transport Temperature
- Room temperature. If transport time will exceed 48 hours: Refrigerated.
- Unacceptable Conditions
- Patient History Form is available on the ARUP website or by contacting ARUP Client Services.
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Fragile X syndrome, the most common heritable form of mental retardation, is characterized by moderate mental retardation in males and mild mental retardation in females, hyperactivity, perseverative speech, social anxiety, poor eye contact, hand flapping or biting, autism spectrum disorders behavioral phenotype, and connective tissue anomalies. Adult males may have physical findings including: macroorchidism, a long narrow face, prominent ears and jaw, and a single palmar crease.
Incidence: 1 in 4,000 Caucasian males and 1 in 8,000 Caucasian females; unknown in other ethnicities.
Inheritance: X-linked dominant.
Penetrance: Reduced in females.
Cause: Expansion of the FMR1 gene CGG triplet repeat.
Full mutation:>200-230 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 (PCR) followed by size analysis using capillary electrophoresis. Methylation-specific PCR analysis is performed for CGG repeat lengths of 55 or greater. Methylation analysis is used to distinguish between premutation and full mutation alleles.
Analytic Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations.
|Phenotype||Number of CGG Repeats|
|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)