Canadian Genomics Research Project Pointing Indigenous Rare Disease Patients Toward Diagnosis
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Loading... - Blake Thompson
- 20 Mar 2023
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A research project in Canada has helped diagnose more than a dozen Indigenous patients with genetic conditions that they were previously only suspected of having.
Patients learned that they had these genetic conditions as participants in the Precision Diagnosis Study, within which researchers hope to better identify childhood-onset monogenic conditions among Indigenous patients who remained undiagnosed after available clinical testing. The study is part of a broader effort to improve healthcare equity among Canada's Indigenous populations, dubbed the Silent Genomes Project.
The Precision Diagnosis Study, which kicked off in 2018, has enrolled nearly 90 families. Of the 70 families who have received genomic analyses, about one-quarter have received probable or definite diagnoses of a genetic condition, said Anna Lehman, co-lead of the study and an associate professor of medical genetics at the University of British Columbia.
To enroll, participants must self-report as having Indigenous ancestry — First Nations, Métis, or Inuit — and be referred by a medical specialist treating their condition, such as a geneticist or pediatrician. Patients can enroll through a network of genetic health centers in a dozen cities in Canada, and participants submit a blood sample for whole-genome sequencing.
From there, researchers identify variants through a three-step process. First, a genomic analyst prioritizes potentially clinically significant variants from the sequencing data. A medical geneticist then reviews the flagged variants and selects a subset to present to a variant committee composed of the patient's referring physician, the enrollment site's principal investigator, medical geneticists, and genetic counselors. The committee discusses whether there's enough evidence to link the variants to a patient's disorder.
The committee focuses on classifying likely pathogenic and pathogenic variants that are causing a patient's condition, but in some cases, the committee has reported variants of uncertain significance, where it felt "there was a significant possibility that [a variant] could be the cause" of a patient's condition but lacked sufficient evidence to make a more definitive call, Lehman said. "This required a group discussion to come to consensus, rather than having specific criteria in making those decisions," she explained.
When researchers identify possible disease-causing genetic variants, results are returned to the patient's referring physician, who is primarily responsible for sharing the results with the family. In cases where the referring physician is not a geneticist, a genetic counselor from the study team helps communicate the results, too. When possible, the Precision Diagnosis Study organizers coordinate confirmatory genetic testing for participants, the cost of which was covered by the study, Lehman said.
Anecdotally, "families have expressed relief at ending their diagnostic odyssey," she added. Read More…
