Family Member Testing
Test code: FMT001 (1 variant), FMT002 (2 variants), FMT003 (3 variants)
Our Family Member Testing (FMT) service provides targeted testing to the relatives of patients previously tested at Blueprint Genetics and in whom a variant has been identified.
Family Member Testing can be used for:
- Diagnostic testing in affected family members
- Predictive testing in unaffected family members
- Carrier testing in the case of autosomal recessive (AR) and X-linked disorders
- Segregation of variants of uncertain significance (VUS) where appropriate
- Confirmation of research results
FMT takes approximately 3-4 weeks from the time the sample and all required information is received.
Segregation analysis of variants of uncertain significance (VUS)
Segregation of a VUS with disease in a family may allow reclassification of the variant. Typically, we would need to identify the variant in two affected family members and absence of the variant in two unaffected family members if the aim is to reclassify the variant. Every time an FMT result is reported, we take into account all previous samples tested for this specific variant and evaluate it’s classification. Therefore, when testing for the purpose of segregation and potential reclassification, detailed, accurate phenotypic information on all family members participating in the testing and their relationships is required. If FMT testing results in re-classification of the VUS, all patient reports where this variant has been previously identified are updated accordingly, and follow-up Clinical Statements are sent to their ordering health care providers.
If you are interested to learn more about the successful impact of family member testing in resolving VUS, read about the study that re-classified the JPH2 p.(Thr161Lys) variant from VUS to pathogenic.
How to order?
Index patient was tested at Blueprint Genetics
When placing a Family Member Test (FMT) order:
- Select FMT in Nucleus or on the paper requisition form
- Include the Order ID, name and date of birth (DOB) or social security number (SSN) of the index patient previously tested at Blueprint Genetics
If the sample from the index patient or other family member is available at Blueprint Genetics, it will be used as a positive control. If the positive control sample has been discarded (patient or guardian did not consent to long-term storage), we will proceed with FMT without the positive control. Please note that the default period of sample storage is one year. Patients/guardians have the option to consent to longer term storage on the consent form.
Index patient was tested at another laboratory
If the index patient was not tested at Blueprint Genetics, the following must be provided:
- Detailed information about the variant including the gene and the nucleotide change (ex. c.123G>A) and/or the amino acid change (ex. Ala123Pro).
- The genomic coordinates of the variant or the specific transcript (NM_number) in cases where several transcripts exist for the gene of interest. This information is typically provided on the index patient report.
- A positive control is strongly recommended.
- A copy of the report is strongly recommended.
FMT can be performed without positive control if sufficient information is provided and the associated limitations are understood.
Is a positive control required for Family Member Testing?
Ideally, FMT is performed alongside a positive control from the index patient to ensure the variant can be detected with the primers used. Please provide a positive control sample from the index patient whenever possible. If a positive control sample is not available from the index patient, a sample from another family member who has tested positive for the variant can be used.
Why is a positive control sample important?
When FMT is performed without a positive control, there is a small chance that the variant is present but not detected leading to a false negative result.
Family Member Testing is possible in the following situations only if the index patient has been tested at Blueprint Genetics and a positive control is available:
- The variant is located in a region that is challenging to analyse, for example, a region with segmental duplication. Read more: blueprintgenetics.com/pseudogene.
- FMT for copy number variants (CNVs). The technology used to confirm CNV findings (qPCR) is very sensitive to sample quality. Testing without a positive control sample may substantially influence the interpretation of the copy number and therefore a positive control sample is required to ensure quality of the testing.
- FMT of prenatal samples.
I do not have access to a positive control. Can I still order FMT for my patient?
If you cannot provide a positive control sample, we can perform FMT without one, with a few exceptions listed above.
As part of our commitment to quality and transparency, the Clinical Statement will indicate that the testing was done without positive control. All negative test results will include a disclaimer stating that a positive control was not provided and the associated risks and limitations.
Please don’t hesitate to contact our Support team with any questions or concerns.
Number of mutations
Accepted sample types
- EDTA blood, min. 1 ml
- Purified DNA, min. 3μg* in TE buffer or equivalent
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.