Misattributed parentage identified through diagnostic exome sequencing: Frequency of detection and reporting practices. Issue 3 (26th November 2021)

• Record Type: Journal Article
• Authors: Stefka, Julie; El‐Khechen, Dima; Cain, Taylor; Blanco, Kirsten; Feldmann, Benjamin; Towne, Meghan C.; Hagman, Kelly D. Farwell
• Is Part Of: Journal of genetic counseling. Volume 31:Issue 3(2022)
• Page Start: 631
• Page End: 640
• Publication Date: 2021-11-26
• Subjects: ethics -- exome sequencing -- misattributed parentage -- misattributed relationships -- non‐paternity -- secondary findings; Genetic counseling -- Periodicals; 616.042
• DOI: 10.1002/jgc4.1530
• Languages: English
• ISSNs: 1059-7700

Abstract

Abstract: Access to genetic testing, namely, diagnostic exome sequencing (DES), has significantly improved, subsequently increasing the likelihood of discovering incidental findings, such as misattributed relationships and specifically misattributed parentage (MP). Until the recently published ACMG statement, there had been no consensus for laboratories and clinicians to follow when addressing such findings. Family‐based genomic testing is valuable for accurate variant interpretation but has the potential to uncover misattributed familial relationships. Here, we present the first published data on the frequency of MP identified through DES at a clinical laboratory. We also investigated clinicians' decisions on how to proceed with analysis, reporting, and disclosure. A database of 6, 752 families who underwent parent‐proband ('trio') DES was retrospectively reviewed for molecular identification of MP and clinicians' MP disclosure decisions. Among 6, 752 trios, 39 cases of MP were detected (0.58%). Non‐paternity was detected in all cases, and in one instance, non‐maternity was also identified. All clinicians decided to proceed by omitting the MP individual from the analysis. Clinicians chose to proceed with duo analysis (87.2%), modify information on the report (74.4%), and communicate MP results to the mother (71.8%), suggesting a trend toward not disclosing to the putative father or proband. The data show that trio DES involves a chance of detecting MP and that clinician disclosure practices do not appear to routinely include direct disclosure to the putative father. MP identified in our parent‐proband trios sent in for DES is lower than the reported frequency of MP in the general population due in part to ascertainment bias as families with known or suspected MP are presumably less likely to pursue trio testing. These data may inform laboratory policies and clinician practices for addressing incidental findings such as MP. Abstract :