Misattributed parentage identified through diagnostic exome sequencing: Frequency of detection and reporting...

Area of Science:

• Genetics
• Genomic Medicine
• Clinical Diagnostics

Background:

• Diagnostic exome sequencing (DES) is increasingly accessible, leading to more incidental findings.
• Misattributed parentage (MP) is a potential incidental finding in family-based genomic testing.
• Lack of consensus existed for handling MP findings until recently.

Purpose of the Study:

• To determine the frequency of MP detected through DES in a clinical setting.
• To investigate clinician practices regarding analysis, reporting, and disclosure of MP findings.
• To provide data informing laboratory policies and clinical practices for incidental findings.

Main Methods:

• Retrospective review of a database of 6,752 parent-proband ('trio') DES cases.
• Molecular identification of MP.
• Analysis of clinician decisions on MP disclosure and reporting.

Main Results:

• MP was detected in 39 out of 6,752 trios (0.58%).
• Non-paternity was identified in all MP cases; non-maternity in one case.
• Clinicians typically omitted the MP individual from analysis, modified reports, and informed the mother, often not disclosing to the putative father or proband.

Conclusions:

• Trio DES has a detectable frequency of MP, albeit lower than general population estimates due to ascertainment bias.
• Current clinician practices suggest a trend towards limited disclosure of MP findings, particularly to the putative father.
• These findings highlight the need for standardized policies for managing incidental MP results in clinical genomic testing.