Molecular Genetics Disorders of Sex Development Panel

Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, and phenotypic sex are discordant. This heterogeneous group of disorders have phenotypic variability and can be challenging to diagnose. This panel is designed to evaluate for individuals with isolated or syndromic disorders of sexual development, which can include ambiguous genitalia, genitourinary (GU) anomalies, gonadal dysgenesis, or hypogonadotropic hypogonadism.

The results from genetic tests can facilitate assessment of levels of risk for patients and lead to more efficient and appropriate medical management. It is recommended that this testing be accompanied by a complete family history and genetic counseling.

Reasons for Referral:

• Molecular confirmation of a clinical diagnosis of DSD

• To aid in decision-making for treatment and management of individuals with DSD.

Next generation sequencing (NGS) will analyze the exons or coding regions of 107 Disorders of Sexual Development-associated genes using Illumina NextSeq 500/550 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.

Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.

Blood: EDTA or ACD (Solution A or B):

• Adult: 5 mL

• Child: 5 mL

• Infant: 2-3 mL

Saliva: 2 ORAgene™ Saliva Collection Kit(s) (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Saliva Collection Kit(s) (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks

Prenatal:

• Direct Amniotic Fluid (10-20mL)

• Direct CVS

• Direct POC

• Cultured Amniocytes (2-T25 flasks

• Cultured CVS (2-T25 flasks)

• Cultured Fetal Tissue: Product of Conception (2-T25 flasks)

• Cord Blood (1-2 mL)

DNA: 10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on Pretnatal Specimens:

• Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test. 

For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Weekly

8 weeks

• Package and ship specimen to remain cold, but not frozen. 
• Ship via overnight express, using the FedEx priority overnight label provided. 
• Contact Client Services for shipping kits and instructions at (855) 535-1522.

1. Eggers, S., Sadedin, S., van den Bergen, J.A. et al. Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort. Genome Biol 17, 243 (2016).

2. Lee PA, Houk CP, Ahmed SF, Hughes IA. Consensus Statement on Management of Intersex Disorders. Pediatrics. (2006).