GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone: 301-519-2100
Fax: 301-519-2892
E-mail: genedx@genedx.com
www.genedx.com
Test Information Sheet
SRY Gene Analysis in 46,XY Gonadal Dysgenesis
Also known as: Testis-Determining Factor (TDF/TDY); Swyer Syndrome
Mendelian Inheritance in Man Number: 400044 (XY Gonadal Dysgenesis); 400045 (SRY-Positive XX Gonadal
Dysgenesis); 480000 (SRY gene)
Clinical features:
46, XY complete gonadal dysgenesis (CGD) is marked by lack of testicular development, streak gonads, the
presence of well-developed Mullerian structures (a uterus and fallopian tubes), underdeveloped breasts, and
female external genitalia. Individuals with 46,XY CGD are typically raised female and present at puberty with
amenorrhea and the absence of secondary sexual characteristics. However, the diagnosis may be suspected in
utero due to an inconsistency between karyotype (46,XY) and ultrasound findings (female). In rare cases, SRY
mutations have been associated with 46,XY partial gonadal dysgenesis (also called 46,XY disorder of sex
development or 46,XY DSD). 46,XY DSD is characterized by the presence of ambiguous genitalia, dysgenetic
testes, and absent to fully developed Mullerian structures. Both 46,XY CGD and 46,XY DSD are associated with
an increased incidence of gonadoblastoma and germinoma.
46,XY gonadal dysgenesis is a genetically heterogeneous disorder with autosomal, X-, and Y-linked forms
(Sarafoglou et al., 2000). The Y-linked form is caused by mutations or deletions of the SRY gene (also known as
TDF or testis determining factor), which is located on chromosome Yp11.3. Typically, the Y-linked form of XY
complete gonadal dysgenesis is sporadic, although approximately 30% of all identified SRY mutations are
inherited (Hawkins et al., 1995). GeneDx also offers sequencing of the NR5A1 (SF-1) gene, which causes
autosomal dominant 46,XY gonadal dysgenesis with or without adrenal insufficiency.
GeneDx also offers SRY FISH to determine the presence or absence of the SRY gene in individuals with 46,XX
testicular DSD who have a 46,XX karyotype and ambiguous or normal male external genitalia with two testicles,
azoospermia, and absent Mullerian structures.
Inheritance pattern: Y-Linked
Reasons for referral:
1. Confirmation of clinical diagnosis
2. Inconsistency of gender identification between karyotype and ultrasound findings
3. Genetic counseling in family members and parents of an affected child
Test method:
GeneDx offers SRY FISH analysis for individuals with 46,XY gonadal dysgenesis or 46,XX testicular DSD to
determine whether the SRY gene is present or absent. For individuals with 46,XY gonadal dysgenesis, bidirectional sequence analysis of the entire coding region of the SRY gene is available using genomic DNA
obtained from buccal (cheek) brushes or blood (1-5mL in EDTA).
Test sensitivity:
Approximately 20-30% of individuals with 46,XY CGD harbor a deletion or a mutation of the SRY gene.
Specifically, deletions of the SRY gene detectable by FISH, PCR, or other methods are identified in 1015% of individuals with 46,XY CGD, and an additional 10-15% of individuals with 46,XY CGD have a
mutation identifiable by sequencing (Scherer et al., 1998). Rarely, mutations of the SRY gene have also
been identified in individuals with 46,XY DSD (Hawkins et al., 1992; Tagliarini et al., 2005; Paris et al.,
2007).
In approximately 80% of individuals with 46,XX testicular DSD, the presence of the SRY gene is
confirmed by FISH or other methods (Vilain 2009). The SRY region is typically present on the X
chromosome. In the remaining 20% of cases, the cause of 46,XX testicular DSD is typically not known.
Mutation spectrum:
Information Sheet on XY Gonadal Dysgenesis
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© GeneDx Revision Date: 12/2012
The SRY gene contains no introns and produces a 900-base-pair transcript. Complete deletions of the SRY gene
are identifiable by FISH or other methods. They occur due to abnormal X-Y recombination during paternal
meiosis, resulting in the replacement of the normal Yp chromosome material with chromosome material from Xp.
In individuals with 46,XY CGD, the majority of SRY mutations identifiable by sequencing are missense or
nonsense substitutions located within the high mobility group (HMG) box domain of the gene, although small
deletions and insertions have also been reported (Cameron et al., 1997). In contrast, SRY mutations in individuals
with 46,XY DSD are typically located outside of the HMG box in the 5’ or 3’ end of the gene, although a mutation
in the HMG box has been reported (Paris et al., 2007).
Specimen Requirements and Shipping/Handling:
 Blood: A single tube with 1-5ml whole blood in heparin (green top tube) for FISH analysis and/or a single tube
with 1-5 mL whole blood in EDTA (lavender top tube) for sequencing. Ship overnight at ambient
temperature, using a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.
 Buccal Brushes: Can be used as an alternative to blood for SRY sequencing only. When sending a buccal
sample, use a GeneDx buccal kit only (others not accepted). Submit by mail. Buccal brushes are not accepted
on children under 6 months of age.
 Prenatal Diagnosis: For prenatal testing for a known mutation in the SRY gene, please refer to the
specimen requirements table on our website at: http://www.genedx.com/test-catalog/prenatal/. Ship
specimen overnight at ambient temperature, using a cool pack in hot weather.
Required Forms:
 Sample Submission (Requisition) Form – complete all pages
 Payment Options Form or Institutional Billing Instructions
*For FISH or FISHonChipDx testing, please use our Molecular Cytogenetics Sample Submission Form available
at: http://www.genedx.com.
Possible ICD9 Codes: Intermediate Sex: 752.7
For test codes, prices, CPT codes, and turn-around-times, please refer to the “46,XY Gonadal Dysgenesis”
page on our website: www.genedx.com
References Cited: Sarafoglou et al., (2000) J Clin Endocrinol Metab 85:483-493. Hawkins, J. (1992) Am J Hum Genet
51: 979-984. Scherer et al., (1998) Cytogenet Cell Genet 80:188-192. Tagliarini et al., (2005) Braz J Med Bio Res
38:17-25. Paris et al., (2007) Fertil Steril 88:1437e21-25. Cameron, et al., (1997) Hum Mutat 9: 388-395. Vilain
(Updated May 2009).46,XX Testicular Disorder of Sex Development. In: GeneReviews at GeneTests: Medical
Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available
at http://www.genetests.org. Accessed [April 2010].
Information Sheet on XY Gonadal Dysgenesis
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© GeneDx Revision Date: 12/2012