5 alpha reductase deficiency; 5ARD.

5-α reductase deficiency is characterized by feminization of the external genitalia in individuals with an 46,XY karyotype and can range from normal female genitalia to undermasculinized genitalia. Individuals with classic 5-α reductase deficiency present at birth with ambiguous genitalia characterized by perineoscrotal hypospadias with pseudovagina, microphallus, and cryptorchidism. 

5-α reductase deficiency is an autosomal recessive disorder caused by mutations in the SRD5A gene. Nucleotide substitutions and small deletions account for the vast majority of mutations described to date. 

1)       Confirmation of diagnosis:

• Patients with clinical findings consistent with 5-α reductase deficiency.
• Test requested by an Endocrinologist or Medical Geneticist.

2)      Carrier testing:

• Carrier testing is not-generally indicated unless a couple is at increased risk of having an affected child, and this information is warranted for risk prediction and/or consideration of reproductive options.  Examples include:
  • Couples where one member of the couple has a family history of 5-α reductase deficiency and the other partner is of an ethnicity with an increased incidence of 5- α reductase deficiency;
  • Couples who have a previously affected child with confirmed 5-α reductase deficiency, when warranted for reproductive decision making.

Bidirectional Sanger sequencing of the coding sequence and flanking intronic sequences of the SRD5A gene.

NM_000348.3 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.