Fragile X (FMR1) with Reflex to Methylation Analysis, Fetal
Prenatal test for fetuses of mothers with fragile X premutations or full mutations.
Polymerase Chain Reaction (PCR)/Capillary Electrophoresis
if culture is required, an additional 1 to 2 weeks is required for processing time.
New York DOH Approval Status
Fetal Cultured Amniocytes or Cultured CVS AND Maternal Whole Blood Specimen : Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).
Cultured Amniocytes or Cultured CVS: Transfer cultured amniocytes or cultured CVS to two T-25 flasks at 80 percent confluence (Min: one T-25 flask at 80 percent confluence). Backup cultures must be retained at the client's institution until testing is complete. If ARUP receives a sample below the minimum confluence, Cytogenetics Grow and Send (ARUP test code 0040182) will be added on by ARUP, and additional charges will apply. If clients are unable to culture specimens, Cytogenetics Grow and Send should be added to initial order.
Maternal Whole Blood Specimen: Transport 2 mL whole blood. (Min: 1 mL)
Cultured Amniocytes or Cultured CVS: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of collection due to viability of cells.
Maternal Whole Blood Specimen: Room temperature.
Cultured Amniocytes or Cultured CVS: Room temperature: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Whole Blood Specimen: Room temperature: 7 days; Refrigerated: 1 month; Frozen: Unacceptable
Background information for Fragile X (FMR1) with Reflex to Methylation Analysis, Fetal
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.
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.
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 55 or greater 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: Methylation patterns may not be fully established in early gestation; thus, diagnostic testing on chorionic villus samples is not recommended. 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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Phenotype||Number of CGG Repeats|
Laboratory Developed Test (LDT)
If a CGG repeat of 55 or greater is detected by PCR and Capillary Electrophoresis; methylation analysis will be added. Additional charges apply.
81243; 81265 Fetal Cell Contamination (FCC); if reflexed, add 81244
|Component Test Code*||Component Chart Name||LOINC|
|0050548||Maternal Contamination Study Fetal Spec||59266-7|
|0050556||Fragile X Allele 1||45321-7|
|0050558||Fragile X Allele 2||45322-5|
|0050559||Fragile X Methylation Pattern||41107-4|
|0050612||Maternal Contam Study, Maternal Spec||66746-9|
|0051389||Fragile X Fetal Specimen||66746-9|
|2010041||Fragile X Interpretation, Fetal||36914-0|
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