- 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
- 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: PCR and Southern blot hybridization. Methylation analysis is performed to distinguish between premutation and full mutation alleles. The sex chromosome gene amelogenin is used to confirm gender but also may indicate the possibility of X chromosome aneuploidies such as Klinefelter or Turner syndrome.
Analytic Sensitivity and Specificity: 99 percent
Limitations: Analytic sensitivity may be compromised by PCR primer site mutations. 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|
- Fragile X tremor ataxia syndrome
- Inherited Mental Retardation
- Martin-Bell Syndrome