What is the purpose of this study?

The purpose of this study is to assess the benefits of mainstreaming whole exome sequencing (WES) by having a non-genetics specialist initiate this process at the start of a patient’s work-up for an IEM or other rare genetic condition. Some of the outcomes we will be assessing include: time to genetic results/diagnosis, time to treatment, changes in clinical management, impact on family planning and familial testing, and quality of care/participant experiences.

Which patients are eligible for the study?

We are accepting patients of all ages. The inclusion criteria are that:

1. A genetic etiology is the likely basis for the patient’s medical and/or family history
2. The patient has multisystem involvement, progressive clinical course, or unexplained non-syndromic single organ indications (e.g., children with retinopathy, liver failure, kidney disease, intractable seizures)
   • Note: This criterion is intentionally broad – if you suspect that an “OMICS First” approach with whole exome sequencing (WES) may benefit your patient, we encourage you to refer.
3. The differential diagnosis is not likely to be addressed by a single-gene test or multi-gene panel
4. WES will impact patient’s management by limiting invasive testing, preventing contraindicated treatments, changing surveillance, informing reproductive decision-making, and/or enabling genetic counselling and testing of family members

Patients can be referred to the study directly from their specialist, whether or not they have already been referred to or seen by Genetics & Metabolism.

How do I refer a patient to the study?

You can download the study referral form and email it to cpmn@umanitoba.ca or fax it to 204-789-3907.

What happens after my patient is referred to the study?

Our study team will review your referral. If the patient is likely eligible (i.e., likely to have an IEM or other rare genetic condition), a member of the study team will call your patient and arrange a meeting to obtain informed consent.

After a patient consents to the study, we will review their case as a group at our “OMICS First” Committee meeting to determine whether WES through MGM should be pursued. You and your team will be invited to attend this meeting.

We will collect blood samples (or use banked DNA samples) from patients who qualify for WES through MGM. Once the samples arrive at the lab, results will take 4-6 months. Once your patient’s results are available, the study team will contact you to discuss the results and a plan for disclosure.

What happens if the study finds a diagnosis for my patient?

We will share the results with you and discuss next steps in the patient’s clinical care. Our team is available to disclose the results or join you in disclosing the results to your patient. We may recommend that you refer your patient to the Program of Genetics & Metabolism (if not already done). Because the results of DNA testing can be worrisome or stressful, patients will have access to an MGM genetic counsellor.

Will you return incidental findings?

Incidental findings (IFs) are unexpected disease-causing variants unrelated to the reason for referral/testing. The genetic testing offered through our study is targeted to each patient’s phenotype; therefore, we will not purposely search for IFs. However, we still anticipate that IFs will be discovered in a minority of participants.

We will discuss IFs during the consenting process, including any opportunities to opt-out of receiving IFs, and will disclose any IFs that are included in the final report. In general, disclosure of IFs will follow the Canadian College of Medical Geneticists 2015 Position Statement, and as such, may be handled differently in children, dependent adults, and competent adults according to the policies of the testing laboratory.

How long will it take to get results?

Once the samples arrive at the lab, results will take 4-6 months.

What happens if no disease-causing variants are found through the study?

You will receive a copy of the genetic test report for your patient. We will also communicate recommendations and possible next steps to you, which may include a referral to the Program of Genetics & Metabolism (if not already done). Our team is available to disclose the results or join you in disclosing the results to your patient.

What happens if my patient is not eligible for genetic testing through the CPMN study?

In some cases, a patient may be deemed ineligible for the “OMICS First” approach offered through MGM. Patients who are deemed ineligible for genetic testing through MGM will be included in the MGM database for our statistical analyses (as explained to patients during the consent process). We may recommend that your patient be referred to the Program of Genetics & Metabolism (if not already done).

What if my patient wants to withdraw from the study?

Patients are free to withdraw from the study at any time. If your patient would like to withdraw from the study or have their sample returned/destroyed, please ask them to contact the study team directly.

What is the purpose of this study?

The purpose of this study is to validate a “Multi-OMICS” pipeline, which will incorporate bioinformatics, transcriptomics, proteomics, metabolomics, Drosophila (fruit fly) models, and induced Pluripotent Stem Cell (iPSC) studies as a way to increase diagnostic yields from whole exome sequencing (WES).

How do I refer a patient to the study?

You can download the study referral form and email it to cpmn@umanitoba.ca or fax it to 204-789-3907.

What happens after my patient is referred to the study?

The study team will review the information provided by the referring health care provider and present to the “Multi-OMICS” committee. If the committee determines one or more “Multi-OMICS” modalities are indicated, the patient will then meet with a member of the study team either in-person, over the phone, or by video call. We will explain the steps of the study and possible benefits and harms of joining, as well as answer any questions the patient has. After a patient consents to the study, we will notify the referring specialist of the “Multi-OMICS” modalities to be pursued.

The patient will be assigned a study ID. If necessary, we will collect blood, urine, and/or a skin sample (or use banked DNA) from patients who qualify for whole genome sequencing, transcriptomics, proteomics, metabolomics, and/or iPSC studies. The sample(s) will then be provided to the academic collaborator(s) for analysis.

The study team will invite you and your team to attend a meeting to discuss your patient’s results. Following this meeting, we may arrange an appointment to disclose the results to your patient and discuss next steps in their clinical care, or we may recommend that you share the results with your patient with the support of an MGM genetic counsellor.

How long will it take to get results?

Generally, the studies may take 6-12 months to complete.

What happens once results are received for my patient?

We will provide a research report summarizing your patient’s results. We will also communicate clinical recommendations and next steps to you.

Our team is available to disclose the results or join you in disclosing the results to your patient. We may recommend that you refer your patient to the Program of Genetics & Metabolism (if not already done). Because the results of DNA testing can be worrisome or stressful, patients will have access to an MGM genetic counsellor.

What if my patient wants to withdraw from the study?

Patients are free to withdraw from the study at any time. If your patient would like to withdraw from the study or have their sample returned/destroyed, please ask them to contact the study team directly.