Genetics Laboratory frequently asked questions

What sample types/volumes are accepted for a particular test?

Refer to the testing services available to search for a particular test requested. Please contact the laboratory if you are still unsure of what sample type/volumes are acceptable.

What are the transport requirements for a particular sample type?

Refer to the sample requirements and shipping to search for a particular sample type. Please contact the laboratory if you are still unsure of what sample type is acceptable.

What solid tissue sources are accepted for DNA extraction?

All fresh tissue types (e.g., kidney, skin, liver) are accepted. Tissues which have been formalin-fixed and embedded in paraffin (FFPE) are not accepted.

Products of Conception (POCs), and specimens from intrauterine fetal deaths (IUFDs) and stillbirths must be sent to a Pathology Laboratory, where they will be prepared and then transferred to the Genetics Diagnostic Laboratory for testing if sample fits criteria for testing. Completed requisitions for both the Pathology and Genetics Diagnostic Laboratories are required.

Please note that cytogenetic testing of POCs, IUFDs and stillbirths is a restricted service; POC and IUFD samples for referred for recurrent pregnancy losses will not the accepted, unless there are documented ultrasound findings or congenital malformations.

Please contact the laboratory if you are still unsure if the sample type or clinical indication is acceptable.

What is the turn-around-time for a particular test?

Refer to the benchmark turn-around-times (TAT) for all tests. These are located under each test in our Genetics tests available page.

What is the price for a particular test?

Laboratory fees only apply to individuals who are not covered by OHIP. Please contact our laboratory if you are unsure of billing.

Are samples from outside of Canada accepted?

Due to laboratory licensing and insurance regulations, we are unable to accept samples for genetic testing from outside of Canada.

Visit the Genetic Testing Registry (GTR) to search for a desired test. The GTR provides a central location for voluntary submission of genetic test information by providers.

Is prenatal testing available for a particular test?

Molecular

Prenatal testing is available for most molecular genetics tests listed, with the exception of facioscapulohumeral muscular dystrophy (FSHD), hereditary breast cancer, hemochromatosis and thrombophilia.

Cytogenetic

Prenatal testing is available for most cytogenetic tests, including chromosome analysis, Rapid Aneuploidy Detection (RAD) and metaphase FISH testing. However, genomic microarray analysis and follow up qPCR testing for CNVs detected by genomic microarray analysis are not available for prenatal samples.

What samples are considered urgent?

• Prenatal (amniotic fluid, CVS or cord blood) samples
• Infant less than or equal to 3 months old
• Pregnancy: when patient or patient's partner is pregnant
• Parents of an "in utero" fetus with an abnormal karyotype
• New leukemia diagnoses: AML, ALL and CML
• New or suspected diagnosis or solid tumor or Burkitt/high-grade lymphoma

Please contact the laboratory if you would like a case to be prioritized for any other reason.

For which molecular tests will a DNA sample be accepted?

DNA will be accepted for all molecular tests except FSHD and SMA; note peripheral blood samples older than 3 days will not be accepted for FSHD testing. Refer to testing services available for a complete list of DNA requirements.

When are samples required from both patient and his/her partner?

Please provide both patient samples for a couple who have had:

• A previous pregnancy with structural chromosome abnormality or unusual variant
• Infertility or unknown etiology
• >3 pregnancy losses with the same partner

Please reference the partner's name and date of birth on both requisitions.

When is it appropriate to refer an individual to the Genetics Clinic at CHEO?

The Genetics Diagnostic Laboratory at CHEO will provide molecular and cytogenetic analysis for a select test menu of disorders affecting children and adults.

In contrast, the Genetics Clinic at CHEO offers assessment, counselling and possible follow-up for your patients. The clinic accepts referrals from physicians and other health care providers.

What does the laboratory require to perform familial variant testing?

If the proband was initially tested by the CHEO Genetics Diagnostic Laboratory

Please indicate on the requisition the variant(s) for which familial testing is required and the proband's identifiers (first name, surname, DOB and CHEO pedigree number).

If the proband was initially tested by another laboratory

Please provide a copy of the proband's genetic testing report. Information including the gene, transcript (NM#), c. and p. nomenclature as well as classification are required to ensure testing for the correct variant. Contact the laboratory to discuss a specific case/scenario if a copy of a family member's genetic testing report is not available.

Are positive controls required?

Positive control samples are accepted, but not required in the majority of cases. Please contact the laboratory to see if a positive control is required for your specific case/scenario.

Can familial variant testing be performed for genes that are not routinely tested by the CHEO Genetics Diagnostic Laboratory?

Visit the Genetic Testing Registry (GTR) to search for a desired test. The GTR provides a central location for voluntary submission of genetic test information by providers.

When does your laboratory re-interpret previously reported variants?

The CHEO Genetics Diagnostic Laboratory will provide re-interpretation if the following criteria are met:

• Your patient is found to carry the familial variant
• The variant was previously interpreted by CHEO Genetics Diagnostic Laboratory

AND

• The previous interpretation of the variant was provided by CHEO > 12 months ago OR we have become aware of a significant change in the information used to interpret the variant (e.g. a relevant functional study has been newly published or was not included in the initial interpretation)

Please note: in most cases, the detection of a variant in one additional affected family member would not be sufficient evidence to change the classification of that variant.

If your patient is found to carry the familial variant, but the familial variant does NOT meet the criteria for re-interpretation, then the initial interpretation will be provided on the family member’s genetic testing report.

For variants previously identified by an external laboratory:

CHEO will not provide an updated interpretation. Please contact the external laboratory to request variant re-interpretation.

Providers can also review relevant resources to check for updated evidence that may impact a variant’s classification, including:

• Relevant literature
• ClinVar
• GnomAD

Please feel free to email GeneticsLabCounsellors@cheo.on.ca if you have additional questions.

When is it appropriate to order the pan cardiomyopathy panel (as opposed to a smaller disease-specific panel)?

When the patient has cardiomyopathy or strong clinical suspicion of cardiomyopathy with features overlapping or atypical of conventional disease categories.

It is important to note that the pan cardiomyopathy panel is not a comprehensive arrhythmia panel. If the primary etiology is more suggestive of channelopathy, a comprehensive arrhythmia panel may be better suited. For instance, if a patient has ventricular fibrillation resulting in cardiac arrest at 40 years or less, without a clear etiology identified, the pan cardiomyopathy panel is likely not the most appropriate first step.

Why wouldn't I always order the pan cardiomyopathy panel?

Because of the large number of genes analysed, the pan cardiomyopathy panel is likely to yield a higher number of variants of uncertain clinical significance than the disease-specific panels. These variants can be difficult for the ordering provider and the patient to interpret.

If the patient's disease is consistent with an established cardiomyopathy, an expanded panel is expected to add only limited additional sensitivity [Alfares et al (2015) Genet Med, PMID 25611685].

Can I order just one gene from one of the panels?

Yes, single gene(s) can be requested, as long as these genes were originally offered on a panel. Please select on the requisition “Single Gene Testing” under “Test Requested” and specify the gene(s) you would like tested.

What is microarray testing?

Microarray analysis is a modern technology that is orders of magnitude more sensitive than a karyotype in detecting partial chromosome deletions and/or partial chromosome duplications.

Which patients should be offered a genomic microarray?

Genomic microarray analysis is the recommended first-tier test for intellectual disability, developmental delay, autism spectrum disorders, and congenital abnormalities not suggestive of common chromosome aneuploidies.

Microarray analysis does not detect balanced structural chromosome rearrangements such as translocations and inversions, low-level mosaicism or point mutations.

If a specific microdeletion or microduplication syndrome is suspected, FISH analysis targeting the suspected critical region may be more appropriate. If a chromosome aneuploidy (mosaic or not) is suspected, chromosome analysis could be more appropriate. Please contact the laboratory if you are unsure of what test to order.

Please review additional information for health-care providers prior to ordering testing.

What type of microarray testing is done at CHEO and how long does it take?

The CHEO Genetics Diagnostic Laboratory utilizes the Affymetrix Cytoscan HD assay. Across the genome, deletions and duplications of 50kb or greater are detected. Additionally, results are assessed for long contiguous stretches of homozygosity of 5Mb or greater on autosomes.

The turn-around time for this test is approximately 6 weeks for routine samples.

What type of results can you expect?

Scientific literature and databases used for interpretation of the microarray results are continually growing; however, we currently have limited information on many regions of the genome. Thus, different types of results can be generated:

Abnormal result

Patients with a clearly pathogenic deletion or duplication should be referred to the CHEO Genetics clinic to receive a clinical assessment, appropriate genetic counselling and additional familial studies, when indicated.

Result of unclear significance

Further analyses are required to help in the interpretation of copy number alterations that are likely pathogenic or of unknown significance. The required samples for the proband and their parents will be indicated in the microarray report. It is very helpful and time saving when parental studies are performed prior to, or concurrent with, a referral to the CHEO Genetics clinic.

Long contiguous stretches of homozygosity (LCSH)

LCSH may be identified in a patient whose parents share a common ancestor (identity by descent) or, more rarely, when uniparental disomy is present. The microarray report may include recommendations to investigate the potential clinical significance of LCSH.

Unexpected result (also called incidental or secondary findings)

Rarely, testing may identify a copy number alteration that is not related to the reason for which microarray testing was performed but that could be potentially medically actionable. Patients with an unexpected result should be referred to the CHEO Genetics clinic to receive a clinical assessment, appropriate genetic counseling and additional familial studies as required.

Normal result

A normal result implies that the patient does not have a duplication or deletion larger than the sizes outlined above. Standard chromosomes analysis (karyotype) is not indicated for patients with a normal microarray result. A normal microarray does not rule out mosaicism, genetically balanced rearrangements, smaller deletions or duplications, imprinting defects, uniparental disomy, nor point mutations. A microarray does not address the possibility of a single gene condition. There are many circumstances under which a referral to the CHEO Genetics clinic is appropriate, regardless of the results of microarray.

What samples are recommended for familial follow-up microarray studies?

The required samples for follow-up microarray testing are outlined in the proband's microarray report. A sample from the proband (positive control) is always necessary, unless a suitable sample is already available in the laboratory. Testing will only be initiated when all relevant samples from family members have been received. When ordering follow-up microarray analysis, if the microarray test was not performed at CHEO Genetics Diagnostic Laboratory, copies of the genomic microarray report need to be attached to the referral.

When is it appropriate to request re-interpretation of previously reported variants?

We do not provide re-interpretation of copy number variants detected on microarray.