Ordering Recommendation

Preferred test to diagnose fragile X syndrome and carrier screening in individuals with a positive family history.

Mnemonic
FRAG X PCR
Methodology

Polymerase Chain Reaction/Capillary Electrophoresis

Performed

Sun-Sat

Reported

4-14 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 5 mL whole blood. (Min: 1.5 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval

By report

Interpretive Data

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.
Inheritance:
X-linked.
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
Unaffected <45
Intermediate 45-54
Premutation 55-200
Affected >200

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note

If a CGG repeat of 100 or greater is detected by PCR and Capillary Electrophoresis, methylation analysis will be added. Additional charges apply.

Hotline History
N/A
CPT Codes

81243; if reflexed, add 81244

Components
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
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Inherited Mental Retardation (Fragile X (FMR1) Diagnostic)
  • Martin-Bell Syndrome (Fragile X (FMR1) Diagnostic)
Fragile X (FMR1) with Reflex to Methylation Analysis