Secondary Findings in a Research Cohort: Spectrum and the Indian Perspective.

Abstract

Genomic sequencing identifies both primary findings related to a patient's phenotype and secondary findings (SFs) which are actionable with early intervention. In the Indian population, there is limited data about types and frequencies of SFs as well as on the understanding of patients' perspectives on receiving these findings. We identified P/LP variants in SF genes (ACMG v3.2) from 500 families who underwent research-based exome sequencing at our center. Families were recontacted, and phenotypic diagnostic tests were done for at-risk individuals. In a separate group of families undergoing diagnostic exome sequencing, a questionnaire-based survey assessed parents' perspectives of these findings for themselves and their extended family members. Frequency of SF is 2.2% with 12 P/LP variants identified in 11 families predominantly in genes of the cardiovascular group (6) and cancer group (5). One family had a positive family history compatible with the associated disease. In response to the questionnaire survey of families undergoing diagnostic exome sequencing, the majority of parents supported SF inclusion in proband tests (97.2%) and in themselves (84.7%). While thorough knowledge of all SFs was favored, financial constraints reduced willingness to pay for additional tests. A comprehensive study from Medical Genetics Center in India reporting 2.2% frequency of SF in 81 SF genes. Clinicians should ensure thorough pretest counseling and clear communication on long-term follow-up for phenotype-negative individuals, variable penetrance, expressivity, and differential severity of SFs and stringent variant interpretation. With the surge in genomic diagnostic tests, it is imperative to assess preparedness of the healthcare systems to ensure equitable and sustainable care for all patients.