Invitae Disorders of Female Sex Development Test

Test description

The Invitae Disorders of Female Sex Development test analyzes the SRY gene that is associated with 46,XX disorders of sex development (DSD)/complete gonadal dysgenesis (CGD). This test can be used determine the presence or absence of the SRY gene in a phenotypic male individual who presents with a female karyotype of 46,XX.

Genetic testing of SRY may confirm a diagnosis and help guide clinical management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (1 gene)

46,XX Disorders of Sex Development (DSD)/Complete Gonadal Dysgenesis (CGD)

Patients with 46,XX disorders of sex development (46,XX DSD) have a 46,XX chromosomal complement but are phenotypically male. This disorder is characterized by azoospermia, absence of female Müllerian structures, and male external genitalia that can range from normal to ambiguous. Small testes, gynecomastia, and testosterone deficiency are also observed. If testosterone deficiency is left untreated, patients may also experience erectile dysfunction, sparse body hair, reduced muscle mass, and increased in fat mass; they may also have increased risks for osteopenia and depression.

The SRY gene is the principal gene associated with 46,XX testicular DSD and accounts for approximately 80% of affected individuals. Alterations of SRY are a rare cause of 46,XY DSD but cause up to 15% of 46,XY CGD.

46,XX DSD is not inherited and generally results from a de novo interchange of SRY from the Y chromosome to the X chromosome.

SRY-related disorders of sex development exhibit complete penetrance with variable expressivity.

The prevalence of 46,XX DSD is approximately 1 in 20,000 males.

This test should be considered for individuals with a 46,XX karyotype, ambiguous or male genitalia, azoospermia, and an absence of Müllerian structures.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
SRY NM_003140.2