XSense® Fragile X with Reflex and Chromosome Analysis, Blood

Test Code

16326

CPT Codes
81243, 88230, 88262

Includes

Chromosome Analysis, Blood
XSense®, Fragile X PCR with Reflex (performed at SJC)

Preferred Specimen

5 mL whole blood collected in a sodium heparin (green-top)
--and--
5 mL whole blood collected in an EDTA (lavender-top) tube

Minimum Volume

1 mL heparinized blood (Critical NICU/Neonates 0.5 mL), and
2 mL EDTA or ACD blood

Other Acceptable Specimens

5 mL whole blood collected in a sodium heparin (green-top)
--and--
5 mL whole blood collected in an ACD-A or B solution (yellow-top) tube

Instructions

Collect whole blood in sodium heparin (green-top) and EDTA (lavender-top) tube. Do not freeze whole blood. Do not transfer whole blood to M4.

See Genetics Specimen Collection Section for detailed specimen instructions.

Transport Temperature

Room temperature

Specimen Stability

Room temperature: Preferred
Refrigerated: Acceptable
Frozen: Unacceptable

Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)

Received frozen

Methodology
Screen: Polymerase Chain Reaction with Detection by Capillary Electrophoresis • Culture • Microscopy • Karyotype
Reflex: Methylation PCR

Setup Schedule

Set up: Daily; Report available: 10 days (4 days for PCR and 6 days additional if reflex required)

Reference Range

See Laboratory Report

Clinical Significance

This test panel can be used to detect abnormalities in the FMR1 gene and chromosome abnormalities. Results may be useful for determining the cause of intellectual disability (ID)/developmental delay (DD) and for informing reproductive counseling for individuals with a family history of ID/DD. An increased number of CGG repeats in the FMR1 gene may cause fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI), or fragile X-associated tremor ataxia syndrome (FXTAS) [1]. If an expanded allele (>85 CGG repeats) is detected, methylation analysis will be performed reflexively to help determine premutation or full mutation status. Chromosome abnormalities may be linked to several conditions, including infertility, miscarriage, birth defects, ID, and DD.

FXS is the most common inherited form of ID and typically affects males more severely than females. Full mutations (>200 repeats) cause FXS, while premutations (55-200 repeats) confer an increased risk of FXPOI, for females, and FXTAS, primarily for older males. The reflex methylation analysis helps determinate hypermethylation status, an indicator of FMR1 gene silencing. It can also detect a mosaic condition in which the CGG repeat number is in the full mutation range, but subpopulations of cells have no hypermethylation. Testing for FXS and related disorders may be considered for individuals with ID, DD, autism spectrum disorder, POI, or intention tremor and ataxia [1]. This test can also be used to identify FXS carriers and determine an individual's risk of having a child with FXS.

Chromosome analysis detects trisomies, such as trisomy 21 (Down syndrome), trisomy 13, and trisomy 18, and sex chromosome abnormalities such as Turner (45,X) and Klinefelter (47,XXY) syndromes. Chromosome analysis also detects microscopically visible chromosomal rearrangements, including Robertsonian translocations, reciprocal translocations, inversions, marker chromosomes, and chromosomal mosaicism at or above 14%.

Disorders that cannot be detected with this panel include most microdeletion syndromes, such as DiGeorge, Prader-Willi, Angelman, Williams, and Smith-Magenis; single-gene disorders, such as FXS caused by deletions and point mutations of FMR1; and chromosomal mosaicism below 14%.

Although FXS and chromosome abnormalities are common causes of ID/DD, many other genetic causes can lead to ID/DD. In the absence of clinical suspicion for a specific genetic disorder, a chromosomal microarray analysis (test code 16478) is recommended by the International Standards for Cytogenomic Arrays Consortium as the first-tier cytogenetic diagnostic test for patients with unexplained ID/DD, autism spectrum disorders, or multiple congenital anomalies [2].
The components of this panel are also available separately. The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.

For more information on this test, or other genetic tests that might be appropriate, please contact Quest Genomics Client Services at 1.866.GENE.INFO (1.866.436.3463).

References
1. Spector E, et al. Genet Med. 2021;23(5):799-812.
2. Miller DT, et al. Am J Hum Genet. 2010;86(5):749-764.

The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. Any Profile/panel component may be ordered separately. Reflex tests are performed at an additional charge.