Whole Blood

3 mL whole blood in lavender top tube.

Frozen or heparinized samples.

Deliver to laboratory immediately after collection. Specimen preferred to arrive within 96 hours of collection.

Performed weekly; Varies

14 days upon receipt at reference laboratory

An interpretive report will be provided.

All detected alterations will be evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations. Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Congenital adrenal hyperplasia (CAH), with an incidence rate of one in 10,000 to 18,000 live births, is 1 of the most common inherited syndromes. The condition is characterized by impaired cortisol production due to inherited defects in steroid biosynthesis. The clinical consequences of CAH, besides diminished cortisol production, depend on which enzyme is affected and whether the loss of function is partial or complete.

Please print, complete and submit the Informed Consent for Genetic Testing and the CYP21A2 Gene Testing Patient Information Sheet from Mayo Medical Laboratories with the specimen.

This mailout test requires pathologist approval for orders during inpatient encounters. Mailouts staff will not process order without approval. The pathologist covering mailouts approval can be reached at pager #3724. If approval is given, the name of the pathologist can be selected in the drop-down menu to the right of the approval warning in Epic when ordering the test.

Useful For:
Carrier screening and diagnosis of 21-hydroxylase deficient congenital adrenal hyperplasia (CAH) in individuals with a personal or family history of 21-hydroxylase deficiency, or as follow-up to positive CAH newborn screens and/or measurement of basal and adrenocorticotropic hormone- 1-24 stimulated 17-hydroxyprogesterone, androstenedione, and other adrenal steroid levels.

May be used to identify CYP21A2 mutations in individuals with a suspected diagnosis of 21-hydroxylase deficient CAH when a common mutation panel is negative or only identifies 1 mutation.

In prenatal cases of ambiguous genitalia detected by ultrasound, particularly when the fetus is confirmed XX female by chromosome analysis.

This test code should also be used for known/familial variant analysis for CYP21A2. Due to the complexity of the CYP21A2 locus, site specific testing for known/familial variants is not offered for this gene.

Cautions:
Because of the complexity of the genetic structure of the CYP21A2 locus, and the possibility that a patient's diagnosis may be due to other gene defects, genetic testing results should be correlated carefully with clinical and biochemical data.

This testing strategy is superior to approaches previously used, but may still miss some complex and large-scale genetic rearrangements or deletions, as well as genetic changes in intronic regions or in far upstream or downstream gene-regulatory elements that impair CYP21A2 gene expression. This can lead to false-negative test results.

Rare polymorphisms in primer binding sites can lead to selective allelic drop-out, which can lead to false-negative or false-positive diagnosis.

Patients without genetic evidence for disease-causing CYP21A2 genetic changes may still have CAH, but due to a different enzyme defect. Additional and expanded biochemical steroid profiling is, therefore, recommended if the clinical picture is strongly suggestive of CAH.

Polymerase Chain Reaction (PCR) Amplification/Fluorescent DNA Sequencing and Deletion Detection by Multiplex Ligation-Dependent Probe Amplification (MLPA)

81405 - CYP21A2 Full Gene Analysis
81402 - CYP21A2 Common Variants