SRY-related Disorders of Sex Development via the SRY Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
901 SRY$440.00 81400 Add to Order
Targeted Testing

For ordering sequencing of 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

SRY mutations have been found via DNA sequencing in approximately 10-15% of patients with 46,XY complete or partial gonadal dysgenesis (Paliwal et al., 2011).

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Del/Dup via aCGH

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
600 SRY$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

The detection rate of copy number changes involving the SRY gene in a large cohort of patients is unavailable in the literature because these have been only reported in limited individual cases and are relatively uncommon (Human Gene Mutation Database).

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Clinical Features

The sex-determining region Y (SRY) gene on the Y chromosome plays a pivotal role in testis determination (Berta et al., 1990). Loss-of-function mutations in the SRY gene can cause 46,XY complete or partial gonadal dysgenesis.

The major clinical phenotype caused by SRY mutations is SRY-related 46,XY complete gonadal dysgenesis (OMIM# 400044). 46,XY complete gonadal dysgenesis is also termed Swyer syndrome or 46,XY pure gonadal dysgenesis (Cotinot et al., 2002; Ostrer, 2008). While having a 46,XY karyotype at a chromosomal level as males normally do, patients affected by 46,XY complete gonadal dysgenesis are phenotypically female with functional female genitalia and structures including a vagina, uterus and fallopian tubes. The key feature of these affected women is the replacement of the ovaries by functionless scar tissue due to the lack of proper ovarian development. Lacking sex glands, affected women do not produce sex hormones (estrogen or progesterone), will not undergo puberty and thus are infertile. Most patients are diagnosed during adolescence when primary amenorrhea is revealed. Notably, patients with 46,XY complete gonadal dysgenesis have an increased risk of developing cancer in the underdeveloped gonadal tissue. Gonadal tumors can develop at any age even before a diagnosis of 46,XY complete gonadal dysgenesis during childhood.

46,XY partial gonadal dysgenesis (also termed 46,XY partial testicular dysgenesis) is characterized by ambiguous external genitalia with a wide spectrum of genital ambiguity, dysgenetic testis and a mixture of both Wolffian and Mullerian ducts (McElreavey et al., 1996; Domenice et al., 1998; Cotinot et al., 2002).

The third, but much less frequent, SRY-related DSD is 46,XX sex reversal (OMIM# 400045) caused by translocation of a segment of the Y chromosome containing the SRY gene to the X chromosome. In this condition, patients with a 46, XX karyotype are phenotypically male (Ostrer, 2008). True hermaphroditism is common in patients with this translocation.


46,XY complete or partial gonadal dysgenesis can be caused by mutations in different genes with different inheritance patterns including autosomal dominant (the WNT4 and NR5A1 genes), autosomal recessive (the DHH gene), X-linked (the NR0B1 gene) or Y-linked (the SRY gene) (Paliwal et al., 2011; Ostrer et al. GeneReviews, 2008). In approximately 10-15% of cases, 46,XY complete or partial gonadal dysgenesis is caused by mutations in the sex-determining region Y (SRY) gene on the Y chromosome. The SRY gene plays a pivotal role in testis determination (Berta et al., 1990; Jäger et al., 1990). Genetic aberrations throughout this single exon gene include missense, nonsense, regulatory mutations and small deletion/insertions. Most of these causative mutations are clustered in the region (codons 13 through 82) coding the high-mobility-group (HMG) box, which is responsible for DNA binding and bending (Harley et al., 1994). Deletions or duplications of the segment of the Y chromosome involving the SRY gene have also been reported but are relatively uncommon (Human Gene Mutation Database). Most of the documented SRY causative mutations are de novo, but familial mutations transmitted from mosaic fathers have also been reported (Schmitt-Ney et al., 1995; Isidor et al., 2009).

Testing Strategy

This test involves bidirectional Sanger DNA sequencing of the single exon of SRY. The entire coding region and ~10 bp of flanking non-coding DNA on either side of the single exon will be sequenced. It also includes targeted testing of two regulatory mutations c. -75G>A and c.-130G>C (Human Gene Mutation Database). We can also perform targeted sequencing of a relevant portion of the single exon for a particular variant (Test #100).

Indications for Test

Candidates for this test are patients with 46,XY complete or partial gonadal dysgenesis or 46,XX sex reversal. Testing is also indicated for family members of patients who have known SRY mutations.


Official Gene Symbol OMIM ID
SRY 480000
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Berta, P, Hawkins, JR, Sinclair, AH, Taylor, A, Griffiths, BL, Goodfellow, PN, Fellous, M. 1990. Genetic evidence equating SRY and the testis-determining factor. Nature 348:448-450. PubMed ID: 2247149
  • Cotinot C, Pailhoux E, Jaubert F, Fellous M. 2002. Molecular genetics of sex determination. Semin. Reprod. Med. 20: 157–168. PubMed ID: 12428196
  • Domenice S, Yumie Nishi M, Correia Billerbeck AE, Latronico AC, Aparecida Medeiros M, Russell AJ, Vass K, Marino Carvalho F, Costa Frade EM, Prado Arnhold IJ, Bilharinho Mendonca B. 1998. A novel missense mutation (S18N) in the 5’ non-HMG box region of the SRY gene in a patient with partial gonadal dysgenesis and his normal male relatives. Hum. Genet. 102: 213–215. PubMed ID: 9521592
  • Harley, VR, Goodfellow, PN.. 1994. The biochemical role of SRY in sex determination. Mol. Reprod. Dev. 39:184-193. PubMed ID: 7826621
  • Human Gene Mutation Database (Bio-base).
  • Isidor, B, Capito, C, Paris, F, Baron, S, Corradini, N, Cabaret, B, Leclair, MD, Giraud, M, Martin-Coignard, D, David, A, Sultan, C, Le Caignec, C. 2009. Familial frameshift SRY mutation inherited from a mosaic father with testicular dysgenesis syndrome. J. Clin. Endocrinol. Metab. 94:3467-3471. PubMed ID: 19531589
  • Jäger, RJ, Anvret, M, Hall, K, Scherer, G. 1990. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature 348:452-454. PubMed ID: 2247151
  • McElreavey K, Vilain E, Barbaux S, Fuqua JS, Fechner PY, Souleyreau N, Doco-Fenzy M, Gabriel R, Quereux C, Fellous M, Berkovitz GD. 1996. Loss of sequences 3’ to the testis-determining gene, SRY, including the Y pseudoautosomal boundary associated with partial testicular determination. Proc. Natl. Acad. Sci. U.S.A. 93: 8590–8594. PubMed ID: 8710915
  • Ostrer H. 1993. 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301714
  • Paliwal P, Sharma A, Birla S, Kriplani A, Khadgawat R, Sharma A. 2011. Identification of novel SRY mutations and SF1 (NR5A1) changes in patients with pure gonadal dysgenesis and 46,XY karyotype. Mol. Hum. Reprod. 17: 372–378. PubMed ID: 21242195
  • Schmitt-Ney, M, Thiele, H, Kaltwasser, P, Bardoni, B, Cisternino, M, Scherer, G. 1995. Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers. Am. J. Hum. Genet. 56:862-869. PubMed ID: 7717397
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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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