Androgen Resistence Syndrome; AIS.

Androgen insensitivity syndrome spectrum disorder is characterized by feminization of the external genitalia, abnormal secondary sexual development, and infertility in individuals with a 46,XY karyotype.  AIS can be divided into three categories based on the clinical presentation:

• Complete androgen insensitivity syndrome (CAIS), with typical female external genitalia
• Partial androgen insensitivity syndrome (PAIS) with predominantly female, predominantly male, or ambiguous external genitalia
• Mild androgen insensitivity syndrome (MAIS) with typical male external genitalia

AIS is an X-linked disorder caused by mutations in the Androgen Receptor (AR) gene. Individuals with AIS have normal levels of testosterone and dihydrotestosterone production but are unable to utilize it due to the defect in the androgen receptor. These individuals do not respond to testosterone treatment, in contrast to individuals with 5- α reductase deficiency.  The majority of mutations identified to date have been sequence mutations, although a few whole and partial gene deletions have also been identified.

1)      Confirmation of diagnosis:

• Patients with clinical findings consistent with AIS.
• Test requested by an Endocrinologist or Medical Geneticist

2)      Carrier testing:

• Adult women at risk to be carriers of an AR mutation because they have had a child with, or have a family history of confirmed AIS.

3)      Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):

• Pregnancies known to be at risk of AIS when the AR mutation is known.

Bidirectional Sanger sequencing of the coding sequence and flanking intronic sequences of the AR gene.

NM_000044 The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays). 

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., large genomic deletions/duplications, promoter mutations, regulatory element mutations).

For carrier/predictive testing due to a family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.