Whole exome sequencing for hereditary disorders


Test in Focus

Whole exome sequencing (WES) is a comprehensive, next-generation sequencing evaluation used by Mayo Clinic Laboratories to examine approximately 20,000 genes for variations linked to genetic illness. In this “Test in Focus” episode of the "Answers From the Lab" podcast, Cherisse Marcou, Ph.D., and Marissa Ellingson, M.S., CGC, discuss how this comprehensive test delivers actionable answers on diagnosis, prognosis, and treatment guidance for individuals identified with a hereditary disorder.  

“WES is now a widely-used, standard of care genetic test for patients with suspected underlying genetic disorders that can allow for identification of a specific variant or variants causing the patient's disorder,” Ellingson says. “Making a genetic diagnosis can allow for tailored medical management and treatment for patients and ultimately influence morbidity and mortality.”

Included in the American College of Medical Genetics and Genomics 2021 clinical guidelines, WES is recommended as a first-tier test for individuals with one or more congenital anomalies, as well as for individuals with developmental delay or intellectual disability. WES also is recommended as second-line testing for patients with clinical features or family history of genetic illness but for whom previous genetic studies have been negative.

Our WES evaluation is backed by a team of laboratory scientists, genetic counselors, and clinicians, who are integrated into the clinical practice at Mayo Clinic. WES results are interpreted by genetic disease experts who are available to answer questions about test finding or the need for additional testing.

“Mayo Clinic has a unique expertise to contribute to the understanding of patient’s results because we are truly an integrated practice,” Dr. Marcou says. “We can get input on a patient’s clinical features or the significance of individual variants identified from some of the world’s leading clinical experts in a given condition that are members of our clinical practice.”

Listen to learn more about how WES can elevate outcomes for individuals affected by genetic disorders 

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Testing

Useful information

  • Serving as a first-tier test to identify a molecular diagnosis in patients with suspected genetic disorders, which can allow for:
    • Better understanding of the natural history/prognosis
    • Targeted management (anticipatory guidance, management changes, specific therapies)
    • Predictive testing of at-risk family members
    • Testing and exclusion of disease in siblings or other relatives
    • Recurrence risk assessment
  • Serving as a second-tier test for patients in whom previous genetic testing was negative
  • Providing a potentially cost-effective alternative to establishing a molecular diagnosis compared to performing multiple independent molecular assays
  • Orderable as a singleton, or with family members with CMPRE to increase the diagnostic yeild

Specimen requirements

Submit only 1 of the following specimens:

  • Specimen Type: Whole blood
  • Container/Tube: Lavender top (EDTA) or yellow top (ACD)
  • Acceptable: Any anticoagulant
  • Specimen Volume: 3 mL
  • Collection Instructions:
    • Invert several times to mix blood.
    • Send whole blood specimen in original tube. Do not aliquot.
  • Specimen Stability Information: Ambient (preferred)/Refrigerated
  • Additional Information: If a cord blood specimen is received, MATCC / Maternal Cell Contamination, Molecular Analysis, Varies will be performed at an additional charge.
  • Specimen Type: Skin biopsy
  • Supplies: Fibroblast Biopsy Transport Media (T115)
  • Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
  • Specimen Volume: 4-mm punch
  • Specimen Stability Information: Refrigerated (preferred)/Ambient
  • Additional Information: A separate culture charge will be assessed under FIBR / Fibroblast Culture for Biochemical and Molecular Testing, Tissue. An additional 4 weeks is required to culture fibroblasts before genetic testing can occur.
  • Specimen Type: Cultured fibroblast
  • Container/Tube: T-25 flask
  • Specimen Volume: 2 Flasks
  • Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
  • Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
  • Additional Information: A separate culture charge will be assessed under FIBR / Fibroblast Culture for Biochemical and Molecular Testing, Tissue. An additional 4 weeks is required to culture fibroblasts before genetic testing can occur.
  • Specimen Type: Blood spot
  • SuppliesCard-Blood Spot Collection (Filtration Paper) (T493)
  • Container/Tube:
  • Preferred: Collection card (Whatman Protein Saver 903 Paper)
  • Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card
  • Specimen Volume: 5 Blood spots
  • Collection Instructions:
    • An alternative blood collection option for a patient 1 year of age or older is fingerstick. For infants younger than 1 year, a heel stick should be used. See Dried Blood Spot Collection Tutorial for how to collect blood spots via fingerstick.
    • Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
    • Do not expose specimen to heat or direct sunlight.
    • Do not stack wet specimens.
    • Keep specimen dry.
  • Specimen Stability Information: Ambient (preferred)/Refrigerated
  • Additional Information:
  • Specimen Type: Saliva
  • Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
  • Supplies: Saliva Swab Collection Kit (T786)
  • Specimen Volume: 1 Swab
  • Collection Instructions: Collect and send specimen per kit instructions.
  • Specimen Stability Information: Ambient 30 days
  • Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.

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Barbara J. Toman (@barbaratoman)

Barbara J. Toman

Barbara J. Toman is a Senior Communications Specialist at Mayo Clinic Laboratories. She is also the science writer for Mayo’s Neurosciences Update newsletter, which helps referring physicians to stay informed about Mayo’s treatment and research. Barbara has worked at Mayo Clinic since 2007. She enjoys international travel and cooking.