SRY-Related Differences of Sex Development via the SRY Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
9217 | SRY | 81400 | 81400,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
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.
Genetics
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).
Clinical Sensitivity - Sequencing with CNV PGxome
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).
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).
Testing Strategy
This test provides full coverage of all coding exons of the SRY gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).
It also includes targeted testing of two regulatory mutations c. -75G>A and c.-130G>C (Human Gene Mutation Database).
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).
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.
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.
Gene
Official Gene Symbol | OMIM ID |
---|---|
SRY | 480000 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
46,XX Sex Reversal, Type 1 | 400045 | |
46,XY Sex Reversal, Type 1 | 400044 |
Citations
- 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
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
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.