46,XY Disorder of Sex Development (DSD) via the HSD17B3 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
735 HSD17B3$780.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

The clinical sensitivity of this test is unknown at this time.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 HSD17B3$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features

A Disorder of Sex Development (DSD) refers to a congenital condition in which the development of chromosomal, gonadal, or anatomical sex is atypical (Hughes et al. 2006). Three subtypes of DSD are generally recognized: Sex Chromosome DSD, 46,XX DSD and 46,XY DSD. 46,XY DSD is defined by a normal 46,XY karyotype in conjunction with atypical development of anatomical sex organs. Patients with 46,XY DSD can present with completely undervirilized external female genitalia (Sinnecker type 5), predominately female genitalia (Sinnecker type 4), ambiguous genitalia (Sinnecker type 3), or micropenis and hypospadias (Sinnecker type 2), although the most frequent presentation is with female external genitalia, labial fusion and a blind ending vagina, with or without clitoromegaly (Sinnecker types 5 and 4) (Boehmer et al. 1999). The early fetus possesses all the precursors for both female (Mullerian) and male (Wolfian) reproductive tracts. Induction of the Wolfian tract, including the urethra, prostate, penis and scrotum, relies on the activities of testosterone and dihydrotestosterone (DHT) hormones (Wilson and Davies 2007). Five critical enzymes are required for the biosynthesis of testosterone and DHT from cholesterol, and deficiencies in at least two of these enzymes are known to cause defects in Wolfian induction, and symptoms of 46,XY DSD (George et al.  2010). The 17β-hydroxysteroid dehydrogenase type 3 (17βHSD-3) enzyme, encoded by the HSD17B3 (OMIM 605573) gene, converts Δ4-androstenedione to testosterone, while 5α-reductase type 2 enzyme, encoded by the SRD5A2 (OMIM 607306) gene, converts testosterone to DHT.


Deficiency of the 17βHSD-3 enzyme leads to an autosomal recessive form of Disorder of Sex Development (DSD) in 46,XY individuals (Saez et al. 1971). In 46,XX individuals, however, 17βHSD-3 deficiency has no apparent effect on female sex development, and these individuals present as normal asymptomatic females (Mendoca et al. 1999). To date, at least 27 pathogenic mutations in the HSD17B3 gene have been reported to cause 17βHSD-3 enzyme deficiency (George et al.  2010), all of which are detected by this sequencing test. Most of the mutations are rare, although a few founder mutations have been described for Arab (i.e. p.Arg80Gln) and Dutch (i.e. p.Asn74Thr and c.325+4A>T) populations, and descendants of the Ottoman Empire, including Greek, Turkish and Syrian patients (i.e. c.655-1G>A) (Boehmer et al. 1999).

Testing Strategy

This test involves bidirectional DNA sequencing of coding exons 1-11 of the HSD17B3 gene, plus ~10 bp of flanking non-coding DNA on either side of each exon. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Candidates for this test are undervirilized male infants with normal Wolfian duct structures, absent Mullerian ducts, and normal adrenal steroid biosynthesis or assigned females who unexpectedly virilize at puberty (Lee et al. 2007). High levels of Δ4-androstenedione and low levels of testosterone are also indicative of 1717βHSD-3 deficiency (George et al.  2010).


Official Gene Symbol OMIM ID
HSD17B3 605573
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Testosterone 17-Beta-Dehydrogenase Deficiency 264300


Genetic Counselors
  • Boehmer, A. L., (1999). "17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations." J Clin Endocrinol Metab 84(12): 4713-21. PubMed ID: 10599740
  • George, M. M., (2010). "The clinical and molecular heterogeneity of 17betaHSD-3 enzyme deficiency." Horm Res Paediatr 74(4): 229-40. PubMed ID: 20689261
  • Hughes, I. A. (2006). "Consensus statement on management of intersex disorders." Arch Dis Child 91(7): 554-563. PubMed ID: 16624884
  • Lee, Y. S., (2007). "Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls." Clin Endocrinol (Oxf) 67(1): 20-8. PubMed ID: 17466011
  • Mendonca, B. B., (1999). "17Beta-hydroxysteroid dehydrogenase 3 deficiency in women." J Clin Endocrinol Metab 84(2): 802-4. PubMed ID: 10022457
  • Saez, J. M., (1971). "Familial male pseudohermaphroditism with gynecomastia due to a testicular 17-ketosteroid reductase defect. I. Studies in vivo." J Clin Endocrinol Metab 32(5): 604-10. PubMed ID: 4252809
  • Wilson, C. A., Davies, D. C. (2007). "The control of sexual differentiation of the reproductive system and brain." Reproduction 133(2): 331-59. PubMed ID: 17307903
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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