Gary J. Latham, PhD, is the chief scientific officer at Asuragen, a Bio-Techne brand. The opinions expressed here are his own and not necessarily those of the organization.
The recently updated guidelines on carrier screening issued by the American College of Medical Genetics and Genomics (ACMG) offer a much-needed refresh that significantly expands the number of genes recommended for screening in women who are pregnant or considering pregnancy.
In the past, carrier screening was advised to inform reproductive decisions for just two conditions: cystic fibrosis and spinal muscular atrophy (SMA). Now, the ACMG recommends screening all women with a standardized panel of 113 genes: 97 autosomal recessive genes plus 16 X-linked genes.
Perhaps the most important thing about this expanded list is that clinicians no longer have to make different recommendations based on a patient’s ethnicity, a practice that can overlook actionable findings— especially in patients of non-European ancestry. The next crucial step will be to encourage the American College of Obstetricians and Gynecologists to update their own carrier screening guidelines to amplify ACMG’s position on inclusion with health care providers and payors.
While that policy work is underway, clinical lab teams will have plenty to keep them busy as they consider how best to implement the new recommendations. As someone who has spent much of their career on improving the quality of carrier screening—particularly for some of the most technically challenging genes—I urge all clinical lab professionals to approach these tests with a pan-ancestry model in mind to deliver the most relevant results for every patient.
The devil is in the details, however. For example, it is important that the variant coverage within each gene screened be appropriate for the intended population. This is true for sequencing tests that enrich for selective gene regions, and it is especially true for targeted, non-sequencing tests that represent the bulk of clinical genetic testing. Let me offer two examples to illustrate my point: cystic fibrosis and SMA.
Traditional screening for cystic fibrosis relies largely on the CFTR2 database of more than 350 pathogenic mutations in the CFTR gene. This database includes an impressive 90,000 patients—but about 95 percent of them are of European descent. Unfortunately, people with other ancestries are more likely to get negative results even when they are carriers. By incorporating relevant variants identified through large-scale sequencing of diverse populations in addition to the CFTR2 data, cystic fibrosis tests can now be updated so their results are more accurate for everybody.
For SMA carrier screening, a similar approach—adding specific pathogenic variants identified in diverse populations—has made it possible to improve the quality of results for underserved groups. This is particularly critical since an SMN1 gene duplication that occurs more commonly in people of African descent can be missed by many current tests. A pan-ancestry approach would incorporate this and other variants into the design of a test for more reliable results.
ACMG’s new recommendations pose significant technical and other challenges for laboratories, but I believe we are up for it. Let’s seize this opportunity to shift our thinking on carrier screening and build tests with the right content to give high-quality results to all patients.