Essendrup, Anna

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.

Abstract Career shadowing can be a valuable opportunity for individuals to experience the daily activities of a working professional. However, there is no published research regarding the impact of shadowing for individuals hoping to pursue a career as a genetic counselor (GC) (termed ‘shadowees’). Additionally, little is known about the impact of shadowing on practicing GCs, nor the value of shadowing in the application and admission process for genetic counseling graduate programs. For this study, three independent surveys were developed and sent to three stakeholder groups: shadowees in the Minnesota Genetic Counseling Experience Program, program directors within the Association of Genetic Counseling Program Directors, and members of the National Society of Genetic Counselors. Quantitative and qualitative analyses were performed on responses. The survey of shadowees ( n = 55) found that the majority believed that shadowing had either a ‘very’ or ‘somewhat positive’ impact on their decision to become a GC and on their application to a genetic counseling graduate program (81.8% and 91.3%, respectively). Of the participating program director respondents ( n = 43), the majority indicated that having shadowing experience was either ‘moderately’ or ‘extremely important’ in offering an interview or for acceptance into a graduate program (63% and 56%, respectively). While programs differ in evaluation of shadowing experiences, most program directors indicated that an applicant's ability to speak to their shadowing experience was the most important factor in admissions consideration (71%). Among the GCs surveyed ( n = 325), 69.2% have hosted shadowees; of these, 82.7% indicated that hosting a shadowee decreases their efficiency at work. Despite this drawback, the majority of respondents expressed a willingness and motivation to host shadowees to help the shadowee (64.8%) and to promote the genetic counseling profession (32.6%). These findings suggest the need for additional research and the development of resources for GCs to increase access of career shadowing.

AbstractThis case report underlines the importance of molecular characterization of genomic duplications and other structural variants in the prenatal setting to guide clinical interpretation, genetic counseling, and perinatal medical care.

A fetus harboring a duplication of SMAD2 exons 1-6 presented with dextrocardia and pulmonary hypoplasia. Mate-pair sequencing revealed the duplication to be in inverted tandem orientation to the wild-type SMAD2 allele, disrupting its sequence and decreasing expression. These observations suggest SMAD2 to be responsible for the fetal dextrocardia.