Skip to main content

Conference Program

Subpage Hero

Loading

Exome sequencing utilization and diagnostic rate in an adult genetics clinic

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical-Adult
  • Secondary Categories:
    • Clinical-Adult & Pediatric
Introduction:
Broad genetic testing is now more accessible and clinically valuable. However, exome sequencing (ES/GS) is still not widely used in adult populations due to socioeconomic barriers to access, insurance coverage, and/or limited knowledge of underlying genetic conditions. As a result, many genetic conditions remain undetected throughout life and can have a significant impact on patients and affected family members. There have been many studies on successful application of ES in pediatrics followed by the ACMG’s development of evidence-based clinical guidelines on ES/GS in pediatric patients. However, there are still no recommendations guiding the use of ES in adults.  



The purpose of this study is to collect and analyze the clinical and genetic testing data from electronic health records for patients seen in the Banner University Medical Center Adult Medical Genetics clinic, one of only 2 adult genetics clinics in the state of Arizona serving an ethnically diverse population. By doing so, the study aims to better characterize the usage of ES/GS with a variety of indications and improve our knowledge about diagnosing adult patients with genetic diseases. Given the unique population this clinic serves, this study plans to analyze patient demographics and socioeconomic factors that may contribute to barriers to access.   

Methods:
We conducted a chart review of adult patients evaluated in the Banner University Medical Center Adult Genetics clinic to identify individuals who underwent exome sequencing from 2022 to 2024. For each individual, demographic information, indication for referral, indication for evaluation (classified by specialty) and ES results (further classified as positive, negative or uncertain) were collected. Results were considered “positive” if they completely or partially explained the patient’s phenotype. The diagnostic rate was calculated for all patients and stratified by referring specialty and indication.   

Results:
A total of 87 patients who underwent exome testing were identified with ages ranging from 18 to 77. We recorded patients’ race and ethnicity from the EHR: 78% identified themselves as white, 14% as Hispanic, 5% as Asian, 2% as Black, and 1% as American Indian. Of these, 31 (37%) had a definitive diagnosis from ES, while an additional 24 (28%) had uncertain result (one or more variants of uncertain significance) and 32 (37%) had a negative result. When stratified by reason for referral, the highest diagnostic rate was seen in patients referred for liver disease (66%, n=2/3) followed by neurologic disease (45%, n=15/33), endocrine disease (40%, n=4/10), hematology/oncology (40%, n=2/5), metabolic or mitochondrial (37.5%, n=3/8), cardiovascular disease (14%, 1/7) and connective tissue disorders (8%, n=1/13). The most common referring providers were primary care providers (n=24) followed by neurologists (n=19).  Additional referring specialties included rheumatology, cardiology, dermatology, ENT, hepatology, nephrology, ophthalmology and vascular surgery. For individuals with positive results, P/LP variants were more frequently single nucleotide variants (74%, n=23/31), followed by copy number variants and indels with 13% (4/31) each. Only variants in the LOX gene were determined to be causative variants in more than one individual.  

Conclusion:
In our study, the overall diagnostic rate for exome sequencing in adults is comparable to the rate seen in the pediatric setting and confirmed the higher diagnostic rate seen in adult neurologic conditions when compared to other indications. Interestingly, high diagnostic rates were also observed in individuals with phenotypes related to liver disease and endocrinologic conditions for which multi-gene panels are considered the first-line diagnostic testing modality and for which ES is not commonly used. These findings argue for broader implementation of ES in the adult setting and highlight the utility of a medical genetics evaluation where a complete phenotype can be obtained.  

Agenda

Sponsors