Assessing and Resolving Findings of Sex Chromosome Discordance in Genetic Testing.

Abstract

Background: X and Y chromosome analysis is a critical component of genetic testing, used both diagnostically and as a quality control (QC) metric. Discordances between expected and observed sex chromosome data can arise due to mislabeling, demographic data errors, transplant history, or biological variations. Such discordances pose challenges to laboratories and affect patient care, particularly in marginalized populations and unique clinical contexts.

Methods: We reviewed cases of sex chromosome discordance identified at our laboratory from January 2021 through August 2023. Cases spanned various testing methods and were categorized by the root cause, including mislabeling, sample mix-ups, transgender individuals, stem cell transplants, and unexplained causes. Case outcomes were assessed, and potential resolutions were analyzed.

Results: Among 65 cases identified, the leading cause of discordance was mislabeling (n = 20, 31%), followed by other/not identified (n = 16, 25%), sample mix-ups (n = 13, 20%), transgender individuals (n = 9, 14%), and stem cell transplants (n = 7, 11%). Cases required additional QC processes such as reanalysis, clinician contact, and occasionally sample re-collection. The process extended turnaround times by up to 13 business days. Detailed case reviews highlighted the challenges and implications of managing these discordances, emphasizing the importance of accurate data transmission and inclusive practices.

Conclusion: Using X and Y chromosome data as a QC metric can identify critical errors but also introduces limitations and bias. Improved standardization, inclusive practices, and alternative QC methods are necessary to ensure accuracy and equitable patient care. Collaborative efforts are required to address demographic complexities and reduce testing delays.