PulmZoom: Yield for Targeted Gene Panels in Genetically-Mediated Respiratory Disorders

Targeted gene panels can be used to diagnose and exclude genetic disorders at a lower cost and sometimes shorter turn-around time than exome or genome sequencing. There are limited data on the yield of targeted gene panels for genetically-mediated respiratory disorders.

Review of testing results and chart review was conducted for all patients having received one or more targeted gene panels for interstitial lung disease, mucociliary disorders, and/or pulmonary vascular disease during a 5-year period. Targeted gene panels (PulmZoom) were developed by the Johns Hopkins Genomics DNA Diagnostic Laboratory in conjunction with relevant faculty experts. Testing employed next generation sequencing (NGS) with Sanger sequencing to confirm low-quality and/or complex insertion-deletion variants where appropriate.

A total of 416 subjects received testing between January 2019 - December 2023. 4.1% received test results that confirmed or established a genetic diagnosis. Results from 1.9% of tests suggested a potential diagnosis, while 21.6% received uncertain results, and 72.4% received a negative result. Mucociliary subpanels had the highest yield of definitive or potential diagnoses, including cystic fibrosis, which was the most common disease identified, followed by primary ciliary dyskinesia.

Targeted gene panels can offer assessment of comprehensive lists of genes to aid in the diagnosis of genetically-mediated respiratory disorders. Yield for panels may be increased with selection of suitable patients via subspecialty evaluations through Pulmonology and Genetics. Future research should assess the efficacy of a sequential approach with targeted gene panels and exome analysis versus exome sequencing alone as well as cost/benefit analyses.