[False negatives in exome sequencing for hereditary bronchiectasis: a report of 5 cases and literature review]

Objective: To summarize the diagnostic approach for patients clinically suspected of having hereditary bronchiectasis after negative exome sequencing (ES) results. Methods: We analyzed the causes of false-negative ES results and subsequent genetic diagnostic strategies in five patients with hereditary bronchiectasis admitted to the Department of Pulmonary and Critical Care Medicine at Peking Union Medical College Hospital. A literature review was conducted to refine the diagnostic workflow for patients with clinically suspected hereditary bronchiectasis following after negative ES findings. Results: All five patients were highly suspected or clinically confirmed to have hereditary bronchiectasis, yet their initial ES results were negative. Through ES data re-analysis, genome sequencing (GS) or functional validation experiments, definitive genetic diagnoses were ultimately established. Conclusion: For patients suspected of hereditary bronchiectasis, reanalysis of ES data alongside GS combined with functional validation experiments or RNA sequencing is the preferred strategy following negative ES results.