A75-06 Genetic Counselor-Supported DNA Sequencing for Bronchiectasis: A Mayo Clinic Experience With Diagnosis and Management

Purpose

Bronchiectasis is a condition characterized by chronic cough, recurrent infections, and progressive airway damage that is rising in prevalence. While often idiopathic, a subset of patients have a genetic cause such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD), or alpha-1-antitrypsin deficiency (A1ATD). Genetic causes for bronchiectasis should be considered in patients with diffuse bronchiectasis involving ≥2 lobes, especially in those with early onset of symptoms, recurrent otitis media or chronic rhinosinusitis, infertility, organ laterality defects (e.g., situs inversus), exocrine pancreatic insufficiency or family history of bronchiectasis. Genetic testing may impact management decisions.

Methods

The Mayo Clinic Center for Individualized Medicine developed the Program for Rare and Undiagnosed Diseases (PRaUD) Genetic Testing and Counseling Unit (GTAC) provides abbreviated, point-of-care genetic counseling, and DNA sequencing-based testing. Patients with bronchiectasis evaluated by GTAC underwent exome or genome-based 52-gene panels which included PCD, CF, and A1ATD (SERPINA1)-associated genes. Sequencing panes results were reviewed and interpreted by a multidisciplinary team including genetic counselors, geneticists, and pulmonologists.

Results

From July 2022 to December 2025, 203 patients were identified; 163 patients completed testing (74% female, 93% white). A molecular diagnosis was confirmed in 10.4% (17/163) of cases, with known pathogenic variants identified in RSPH4A, SERPINA1 (A1ATD), and CFTR (CF). Variants of uncertain significance (VUS) were identified in 24% of patients. Notably, 11.6% (19/163) were identified as CF carriers, a rate significantly higher than the general European-ancestry population (∼4%). Clinical management was impacted for two patients, including the initiation of targeted CFTR modulator therapy in one patient with CF-related disorder (CFTRD) and one CFTR pathogenic variant heterozygote.

Conclusions

Genetic counselor-supported DNA sequencing for bronchiectasis led to an increased identification of genes that cause bronchiectasis. Interestingly, we found a high rate of CFTR heterozygote variant carriers in our clinic cohort, this aligns with the findings of other studies that CFTR variant carriers can have an increased frequency of bronchiectasis. The identification of pathogenic variants and VUS helps facilitate a diagnosis or potential genetic cause in a significant proportion of patients and highlights the need for further research in understanding the epidemiology of CF, PCD, and A1ATD-related variant genotypes in patients with bronchiectasis.

Clinical Implications

Comprehensive DNA sequencing, combined with genetic counseling and support from genetic counselors in partnership with pulmonologists can advance precision diagnostics and care for patients with bronchiectasis.

This abstract is funded by: None