Congenital Adrenal Hyperplasia (CAH) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
12053 CYP11A1 81479,81479 Order Options and Pricing
CYP11B1 81405,81479
CYP17A1 81405,81479
CYP21A2 81479,81479
HSD3B2 81479,81479
POR 81479,81479
STAR 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
12053Genes x (7)81479 81405, 81479 $1940 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders each due to defects in a single gene involved in different steps of cortisol biosynthesis (Hannah-Shmouni et al. 2017. PubMed ID: 28476231; Merke and Bornstein. 2005. PubMed ID: 15964450). The clinical consequence of deficient cortisol biosynthesis represents a continuous phenotypic spectrum depending on causative gene, genotype, residual activity and age of presentation. Clinical features of CAH include adrenal insufficiency, genital ambiguity or disordered sex development, infertility, short stature, hypertension, and an increased risk of metabolic syndrome during adolescence and adulthood.

Over 95% of CAH cases are caused by 21- hydroxylase deficiency (21-OHD). The second most common form of CAH is due to 11-hydroxylase deficiency (11-OHD) which accounts for approximately 5% of cases. Other less common forms of CAH include 3β-hydroxysteroid dehydrogenase type 2 deficiency, 17α-hydroxylase deficiency, congenital lipoid adrenal hyperplasia, side-chain cleavage enzyme deficiency, and cytochrome P450 oxidoreductase deficiency (ORD).

Genetics

CAHs are autosomal recessive disorders. The known causative genes are CYP21A2, CYP11B1, HSD3B2, CYP17A1, POR, STAR and CYP11A1. Documented pathogenic variants in these genes include various types of genetic defects, including truncating changes (nonsense, splice variants and frameshift small deletion/insertions), missense substitutions and intragenic large deletions. Complex gene rearrangements are commonly found in the CYP21A2 gene.

Over 95% of CAH cases are caused by 21- hydroxylase deficiency (21-OHD) due to genetic defects in the CYP21A2 gene. Genetic analysis of this gene is complicated by its highly similar pseudogene CYP21A1P and the nature of local surrounding sequence. This region is characterized by relatively frequent homologous recombination events due to the existence of highly paralogous pseudogenes in tandem. Consequently, the pathogenic variants of CYP21A2 include chimeric CYP21A1P/CYP21A2 genes (alternatively called 30 kb deletions in the literature), common pseudogene variants transferred via gene conversions and other rare pathogenic variants. For more details, please see the CYP21A2 single-gene test description.

The second most common form of CAH (~5% of cases) is 11-hydroxylase deficiency (11-OHD) due to genetic defects in the CYP11B1 gene. 11-hydroxylase is a P450 type I mitochondrial enzyme which is responsible for the conversion of 11-deoxycortisol to cortisol, and 11-deoxycorticosterone (DOC) to corticosterone. Due to high sequence similarity with the CYP11B2 gene, which encodes aldosterone synthase, rare chimeric CYP11B2/CYP11B1 genes can also result in CAH due to 11-OHD (Hampf et al. 2001. PubMed ID: 11549691; Duan et al. 2018. PubMed ID: 29703198).

Other less common forms of CAH include 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency, 17α-hydroxylase (CYP17A1) deficiency, congenital lipoid adrenal hyperplasia (STAR), side-chain cleavage enzyme (CYP11A1) deficiency, and cytochrome P450 oxidoreductase (POR) deficiency.

Founder pathogenic variants in different geographic regions worldwide are evident in all of these genes. See individual gene test descriptions for information on the molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Since our test utilizes an integrative strategy via Sanger sequencing to perform a comprehensive evaluation for CYP21A2 (see Testing Strategy in the CYP21A2 test description), the detection rate of pathogenic CYP21A2 variants is expected to be approximately 98% (Krone et al. 2000. PubMed ID: 10720040; Stikkelbroeck et al. 2003. PubMed ID: 12915679; Finkielstain et al. 2011. PubMed ID: 20926536; Krone et al. 2013. PubMed ID: 23337727).

In a study of 28 patients from 24 Turkish families affected by 11-hydroxylase deficiency (26 classic and 2 late-onset), using the strategy of specifically amplifying CYP11B1 gene fragments, all patients received a molecular diagnosis (Kandemir et al. 2017. PubMed ID: 26956189). Similar clinical sensitivity was observed by Bas et al. (2018. PubMed ID: 29626607). These studies indicated intragenic large deletions and chimeric CYP11B2/CYP11B1 genes are rare. Therefore, our test is expected to be able to detect the vast majority of pathogenic variants.

Other genes in this panel have no paralogous sequences in the genome. Therefore, this panel is able to detect over 98% of pathogenic variants for congenital adrenal hyperplasia patients overall.

Testing Strategy

This panel provides full coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

We utilize a long range PCR strategy to specifically amplify the CYP21A2 gene. This “one-stop” strategy is able to capture chimeric CYP21A1P/CYP21A2 genes (alternatively called 30kb deletions in the literature), common pseudogene variants transferred via gene conversions and other rare pathogenic variants. After this test, we don’t recommend additional testing (such as MLPA for deletions), except family follow-up tests. Please see details in the CYP21A2 single-gene test description.

Using the strategy of specifically amplifying CYP11B1 (to avoid the paralogous gene CYP11B2), our strategy is NOT designed to detect rare chimeric CYP11B2/CYP11B1 genes. However, our assay is expected to capture a large portion of small gene-conversion events.

LIMITATIONS OF THIS TEST: A duplicated CYP21A2 gene or a CYP21A2-like gene next to the pseudogene TNXA in the middle of the RCCX module, which is uncommon, CANNOT be detected via the current strategy (Koppens et al. 2002. PubMed ID: 12384784; Kleinle et al. 2011. PubMed ID: 19773403; Tsai et al. 2011. PubMed ID: 21324303). Therefore, test results via the current strategy should always be interpreted in context of clinical findings, family history and other laboratory data.

Our assay also will generally not detect rare chimeric CYP11B2/CYP11B1 genes.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with congenital adrenal hyperplasia (CAH).

Genes

Official Gene Symbol OMIM ID
CYP11A1 118485
CYP11B1 610613
CYP17A1 609300
CYP21A2 613815
HSD3B2 613890
POR 124015
STAR 600617
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®
P450 Oxidoreductase Deficiency via the POR Gene

Citations

  • Bas et al. 2018. PubMed ID: 29626607
  • Duan et al. 2018. PubMed ID: 29703198
  • Finkielstain et al. 2011. PubMed ID: 20926536
  • Hampf et al. 2001. PubMed ID: 11549691
  • Hannah-Shmouni et al. 2017. PubMed ID: 28476231
  • Kandemir et al. 2017. PubMed ID: 26956189
  • Kleinle et al. 2009. PubMed ID: 19773403
  • Koppens et al. 2002. PubMed ID: 12384784
  • Krone et al. 2000. PubMed ID: 10720040
  • Krone et al. 2013. PubMed ID: 23337727
  • Merke and Bornstein. 2005. PubMed ID: 15964450
  • Stikkelbroeck et al. 2003. PubMed ID: 12915679
  • Tsai et al. 2011. PubMed ID: 21324303

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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