Rapid Genotyping to Improve Patient Care

There are many circumstances where waiting for a clinical laboratory test result can lead to a missed opportunity to use the testing results to improve a patient’s care.

Almost all clinical genetic tests have notoriously slow turn-around-times (TAT), usually on the order of weeks to months.

With a goal of creating an approach to improve patient care, the Scharfe lab developed a rapid testing platform in the Yale Department of Genetics in 2019. This PCR-based platform was developed as a response to the typically slow clinical genetic TAT. As demonstrated below, this strategy allows the team to carry out a diagnostic test for a disease associated variant – from fingerstick to result - in less than 30 minutes.

This approach can be employed within the Yale DNA Diagnostic laboratory under CLIA license for clinically important variant detection.

The initial use case for which this novel rapid testing method was validated was for the molecular diagnosis of Transthyretin (TTR) Cardiac Amyloidosis. We are exploring applications for this test in emergency rooms and outpatient settings both in the US and in the developing world. When applied, a rapid TTR diagnostic result is available in as little as 30 minutes for an individual presenting with congestive heart failure (CHF) who may have the West African “founder mutation” (TTR variant c.424G>A, p.V142I) that is present in ~15% of African Americans who present with CHF.

This rapid testing technology is readily adaptable and can be applied clinically to detect genomic variants across the genome.

• Validation of a rapid TTR genotyping assay as a point-of-care tool for cardiac amyloidosis diagnosis in low-income settings (PB1707)
  
• Enrichment for Cases of African-American Patients with Pathogenic TTR V142I Variant in the TOPCAT Trial