Test Id : CMPRG

Skin biopsy or cultured fibroblast specimens:

If a skin biopsy is received, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

This test is not appropriate for affected patients (probands) undergoing whole genome sequencing (WGS). This test is intended to be ordered for biological family member comparator specimens only. For WGS testing for the proband, order WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies. If this test is ordered on a proband, the test will be canceled and WGSDX will be performed as the appropriate test.

If this test is ordered on a family member comparator of a proband having WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies; or WESMT / Whole Exome and Mitochondrial Genome Sequencing, Varies, this test will be canceled and CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies performed as the appropriate test.

Each specimen must be on a separate order.

To order whole genome sequencing for the patient and the family member comparator specimens, see the following steps:

1. Order WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies on the patient (proband).

2. Order this test on all family members' specimens being submitted as comparators.

 a. When available, the patient's biological mother and biological father are the preferred family member comparators.

 b. If one or both of the patient's biological parents are not available for testing, specimens from other first-degree relatives (siblings or children) can be used as comparators. Testing typically includes up to 2 family member comparators. Contact the laboratory at 800-533-1710 for approval to send specimens from other relatives or to send the patient and 3 first-degree relatives (quad).

 c. The cost of analysis for family member comparator specimens is applied to the patient's (proband's) test. Family members will not be charged separately.

3. Collect patient (proband) and family member specimens. Label specimens with full name and birthdate. Do not label family members' specimens with the proband's name.

4. For each family, complete the following portions of the Whole Genome Sequencing: Ordering Checklist. A separate form is not needed for each family member.

 a. Patient Information is required for all clients.

 b. Informed Consent is required for New York State clients.

 c. If the patient wishes to opt-out of receiving secondary findings or change the DNA storage selection, select the appropriate boxes in the Informed Consent section.

5. Attach clinic notes from specialists relevant to patient's clinical features, if available.

6. Attach pedigree, if available.

7. Send paperwork to the laboratory along with the specimens. If not sent with the specimens, fax a copy of the paperwork to 507-284-1759, Attn: WGS Genetic Counselors.

For more information see Whole Exome and Genome Sequencing Information and Test Ordering Guide.

Specimen preferred to arrive within 96 hours of collection.

Whole Genome Sequencing: Ordering Checklist is required for all clients, and Informed Consent is required for New York clients. Fill out one form for the family and send with the specimens.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Submit only 1 of the following specimens for each family member.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

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 CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 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 CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

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 quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

Specimen Type: Muscle tissue biopsy

Supplies: Muscle Biopsy Kit (T541)

Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Instructions.

Specimen Volume: 10 to 80 mg

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

• Muscle Biopsy Specimen Preparation Instructions
• Whole Genome Sequencing: Ordering Checklist
• Whole Exome and Genome Sequencing Information and Test Ordering Guide

1. Whole Genome Sequencing: Ordering Checklist is required.

2. New York Clients-Informed consent is required, included in the above form. Document on the request form or electronic order that a copy is on file.

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Whole blood: 1 mL; Other specimen types: See Specimen Required

Submitting a biological family member's specimen to be used as a comparator for affected patients (probands) undergoing whole genome sequencing

This test is for the biological family members whose specimens are being submitted as comparators for patients undergoing WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies.

Skin biopsy or cultured fibroblast specimens:

If a skin biopsy is received, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

This test uses next-generation sequencing technology to assess the genome of patients with suspected underlying genetic disorders. This information is used to assist in the interpretation of the patient's (proband's) whole genome sequencing results (WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies). Ordering this test on biological family members of the affected proband can help determine the inheritance of genetic variants that are identified and if the variants segregate with a phenotype in the family. Submitting comparator samples from biological family members increases the chance of identifying a diagnosis in the proband. Whole genome sequencing is most informative when samples from both biological parents are used as comparators. Therefore, it is highly recommended that samples are also submitted from the patient's biological mother and biological father.

If more than 2 biological family member comparator specimens are submitted, the additional comparator specimens may not be fully sequenced but rather used for confirmatory presence or absence of identified variants of interest after initial variant calling and review.

An interpretive report will be provided.

Interpretive information will only be provided on the proband's whole genome sequencing report (WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies). The presence of a variant in family member comparator samples is stated on the proband's report. Variants that are present in family member comparator samples but absent from the proband sample are not evaluated or reported.

Secondary Findings:

Patients are evaluated for medically actionable secondary findings and these findings are reported in accordance with the American College of Medical Genetics and Genomics recommendations.(1) The presence of a secondary finding in family member comparator samples is stated on the patient's (proband's) report unless family members opt-out of secondary findings. If the proband opts out, secondary findings will not be evaluated or reported in any family member comparators. Secondary findings that are present in family member comparators but absent from the patient (proband) are not evaluated or reported.

The absence of a reportable secondary finding does not guarantee that there are no disease-causing or likely disease-causing variants in these genes, as review is limited to known or highly suspected pathogenic findings, and not all regions of these genes are adequately evaluated by this technology.

This testing is intended to be used for biological family members whose specimens are being submitted as comparators for affected patients (probands) undergoing whole genome sequencing. Although test results will only be provided in the context of the proband, it is possible for family members serving as comparators to learn unexpected genetic information about themselves. For example, it is possible for individuals to learn that they carry certain genetic variants that are being reported in the proband, or that biological relationships are not as described.

It is not guaranteed that patient data will be stored indefinitely.

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories at 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

A genetic consultation is recommended for patients undergoing this test, both prior to testing and after results are available.

1. Miller DT, Lee K, Gordon AS, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1391-1398

Polymerase chain-reaction-free next-generation sequencing is performed on DNA extracted from the patient (proband) and all applicable comparator samples to test for the presence of variants. The human genome reference GRCh38/hg38 build is used for sequence read alignment. Variants are called using an optimized bioinformatics package. The average genomic coverage is at or above a read depth of 32X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 50 base pairs (bp). This assay also detects greater than 99% copy number variants (deletions/duplications) at least 1000 bp in size. Confirmation of select reportable variants in the proband and submitted comparator samples may be performed by alternate methodologies based on internal laboratory criteria.

There may be regions of genes that cannot be effectively evaluated by sequencing as a result of technical limitations of the assay, including regions of homology, variable depth of coverage, and repetitive sequences.(Unpublished Mayo method)

Varies

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.