Androgen Insensitivity Syndrome (AIS) via the Androgen Receptor (AR) Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7577 AR 81173 81173,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7577AR81173 81173, 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Male sexual differentiation requires the Androgen Receptor (AR) and its ligands—Testosterone and Dihydroxytestosterone (DHT) (Wilson and Davies 2007). Testosterone, which is secreted by the developing testes beginning at 9 weeks of gestation, stimulates Wolffian duct differentiation into epididemis, vas deferens and seminal vesicles. DHT, derived from testosterone via the enzymatic activity of 5α-reductase type 2, stimulates prostate development and masculinization of the primordial external genital into penis and scrotum (Brinkmann et al. 2001). Both androgens exert their effect through binding and activation of the AR. In individuals with a 46,XY karyotype, defects in AR signaling result in Androgen Insensitivity Syndrome (AIS). AIS symptoms range from complete insensitivity (CAIS), whereby patients have female external genitalia, a short, blind ending vagina and no Wolffian duct derived structures, to partial insensitivity (PAIS), whereby patients can have a predominately female appearance with mild cliteromegaly, ambiguous genitalia, or an undervirilized male appearance (Galani et al. 2008). Given the complex nature of genital anomalies, recommendations for treatment and management of AIS should rely on an elaborate and individualized approach (Dacou-Voutetakis 2007). Genetic testing for the molecular cause of AIS is recognized as an invaluable aspect of this approach.

Genetics

Pathogenic variants in the Androgen Receptor (AR) gene are the most common cause of Androgen Insensitivity Syndrome (AIS). To date, over 1,000 pathogenic variants have been described throughout the AR gene (Gottlieb et al. 2012). Nonsense and frameshift pathogenic variants cause complete AIS (CAIS), while weaker pathogenic variants, such as missense and regulatory (i.e. those in the promoter, introns, and 3’ untranslated region) variants, cause more variable symptoms and partial AIS (PAIS). Importantly, all documented AR pathogenic variants, and their respective phenotype, can be found in the Androgen Receptor Gene Mutations Database (ARDB, http://androgendb.mcgill.ca/), making it possible for physicians and genetic counselors to offer a statistically relevant phenotype prognosis for most identified pathogenic variants. The AR gene is located on the X chromosome, so in most cases (~60%) the pattern of inheritance is X-linked recessive. However, an apparently high mutation rate within the AR gene also results in relatively frequent occurrence (~40%) of de novo pathogenic variants and somatic mosaicism (Audi et al. 2010). Identifying patients with de novo pathogenic variants and somatic mosaicism has important consequences for sex assignment and genetic counseling (Kohler et al.2005). Pathogenic variants in AR have been detected in 46,XY females. 46,XX carrier females are often unaffected.

Testing Strategy

This test provides full coverage of all coding exons of the AR gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to identify a pathogenic variant in 65% of all patients with Androgen Insensitivity Syndrome (Boehmer et al. 2001).

Although the clinical sensitivity of deletion/duplication testing is expected to be relatively low, at least eighteen gross deletions/duplications have been reported in the AR gene (Human Gene Mutation Database).

Indications for Test

Candidates for this test are patients with a presumptive diagnosis of AIS (Boehmer et al. 2001).

This test is not designed to quantify the number of CAG or CCG trinucleotide repeats in exon 1, and is not appropriate for diagnosis of patients with Spinal and Bulbar Muscular Atrophy (SBMA).

Gene

Official Gene Symbol OMIM ID
AR 313700
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Androgen Resistance Syndrome XL 300068

Related Test

Name
X-linked Spinal and Bulbar Muscular Atrophy (Kennedy Disease) via the AR Gene CAG Repeat Expansion

Citations

  • Audi L. et al. 2010. The Journal of Clinical Endocrinology and Metabolism. 95: 1876-88. PubMed ID: 20150575
  • Boehmer A.L. et al. 2001. The Journal of Clinical Endocrinology and Metabolism. 86: 4151-60. PubMed ID: 11549642
  • Brinkmann A.O. 2001. Molecular and Cellular Endocrinology. 179: 105-9. PubMed ID: 11420135
  • Dacou-Voutetakis C. 2007. Nature Clinical Practice. Endocrinology & Metabolism. 3: 668-9. PubMed ID: 17724484
  • Galani A. et al. 2008. Hormones (athens, Greece). 7: 217-29. PubMed ID: 18694860
  • Gottlieb B. et al. 2012. Human Mutation. 33: 887-94. PubMed ID: 22334387
  • Human Gene Mutation Database (Bio-base).
  • Köhler B. et al. 2005. The Journal of Clinical Endocrinology and Metabolism. 90: 106-11. PubMed ID: 15522944
  • Wilson C.A, Davies D.C. 2007. Reproduction. 133: 331-59. PubMed ID: 17307903

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

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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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