X-Chromosome Inactivation Analysis
Ordering Recommendation

Use to determine X-chromosome inactivation (XCI) pattern for female carriers of X-linked disorders and assess pathogenicity of genetic variant in an X-linked gene. Test does not detect clonality.

Restriction Enzyme Digestion/Polymerase Chain Reaction/Fragment Analysis
10-14 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL)  
Storage/Transport Temperature
Unacceptable Conditions
Ambient: 3 days; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report
Interpretive Data
Background for X-Chromosome Inactivation Analysis
Females usually have two copies of the X-chromosome, one of which becomes randomly inactivated early in embryonic development in a process known as lyonization. If either the paternally or maternally derived X-chromosome is preferentially inactivated, this results in a non-random or "skewed" pattern of X-chromosome inactivation (XCI). The pattern of XCI may vary among tissue types. XCI ratios of 50:50 to 79:21 are considered random, ratios of 80:20 to 89:11 are moderately skewed and ratios of 90:10 to 100:0 are highly skewed.
Non-random XCI may result by chance or from secondary cell selection in women who are heterozygous for X-chromosome rearrangements, carriers of mutations in X-linked genes, or affected with neoplastic disease.
Gene Tested:
The androgen receptor (AR) gene on the X chromosome.
Clinical Sensitivity:
Approximately 90 percent. An estimated 10 percent of women have skewed X-inactivation by chance. However, skewed XCI may be seen more frequently with increasing age.
Methylation-sensitive restriction digest followed by PCR and fragment analysis.
Testing is limited to XX females only. This assay will be uninformative in up to 20 percent of females due to homozygosity for the polymorphic AR gene locus analyzed. XCI patterns may differ among tissues; therefore, the XCI ratio reported is for the tissue type tested. Although this test will detect the methylation status of the X-chromosomes, it will not determine if the X inactivation pattern is associated with rearrangements of the X chromosome, mutations in X-linked genes or neoplastic disease. If a non-random XCI pattern is present, the parent of origin of the active X cannot be determined without testing parental samples. XCI ratios should not be used to predict prognosis for female carriers of X-linked disorders as variable expressivity may result due to other genetic or environmental modifiers. Because the level of XCI may differ in prenatal specimens and whole blood, this test is not recommended for prenatal diagnosis. Diagnostic errors can occur due to rare sequence variations.

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.
CPT Code(s)
Component Test Code*Component Chart NameLOINC
2006353X-Chromosome Inactivation Specimen
2006354X-Chromosome Inactivation Interpretation
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