An understanding of the role of genomic testing in investigation of disease is rapidly evolving.
Genomic testing may be indicated in the investigation of patients with a Mendelian phenotype or family history which strongly implicates a genetic aetiology. The case for targeted diagnostic testing is clear where the phenotype is consistent with a known disease in which mutations in a number of genes are known to be causative.
Genomic testing may also play a role in the investigation of families with a Mendelian phenotype where the specific genetic aetiology is not established i.e. genome-wide diagnostic testing. It may also play a role in the investigation of multiple affected individuals from different families or single individuals with very rare genetic disorders, where randomised clinical trials to assess clinical utility and other measures of efficacy of genomic testing are not possible. These referrals are based on clinical judgment. This approach is analogous to investigations such as cytogenetic analysis, microarrays or tissue biopsy where the target pathology is unknown.
There is debate about the use of genomic methods in preconception carrier screening for relevant mutations, prenatal screening, and as a first tier approach for newborn screening.
A recent report from the Foundation for Genomics and Population Health in the UK concludes that “Extensive interrogation of genomic data for preventive purpose is not recommended.”
These different purposes of genomic testing involve different ethical considerations as well significant differences in analysis and interpretation. The clinician, laboratory, and patient should have a clear understanding of the purpose and scope of a test, and this should be reflected in pre-test counselling and consent, in the analysis and interpretation, and in the reporting and distribution of a genomic test.