Functional Evaluation and Genetic Landscape of Children and Young Adults Referred for Assessment of Bronchiectasis

• DOI: 10.3389/fgene.2022.933381
• Publication Date: 2022-08-08T08:38:07Z
• Authors: Jeffrey Fong Ting...; Mianne Lee; Martin Man Chun Chui; Mullin Ho Chung Yu; Jasmine Lee Fong ...; Christopher Chun ...; Christy Shuk-Kuen...; Ka Ka Siu; Jacqueline Hung; Kit San Yeung; Anna Ka Yee Kwong; Christopher O'Cal...; Yu Lung Lau; Chun-Wai Davy Lee; Brian Hon-Yin Chung; So-Lun Lee
• Keywords: genome sequencing; 0301 basic medicine; 03 medical and health sciences; transmission electron microscopy; early-onset bronchiectasis; Genetics; primary ciliary dyskinesia; high-speed video microscopy; QH426-470; exome sequencing; 3. Good health

Bronchiectasis is the abnormal dilation of airway which may be caused by various etiologies in children. Beyond more recognized cause bacterial and viral infections primary immunodeficiencies, other genetic conditions such as cystic fibrosis ciliary dyskinesia (PCD) can also contribute to disease. Currently, there still debate on whether genome sequencing (GS) or exome reanalysis (rES) would beneficial if initial targeted testing results returned negative. This study aims provide a back-to-back comparison between rES GS explore best integrated approach for functional genetics evaluation patients referred assessment bronchiectasis. In phase 1, an 60 were analyzed (ES) with one additional individual recruited later affected sibling ES. Functional nasal nitric oxide test, transmission electron microscopy, high-speed video microscopy conducted when possible. 2, was performed 30 selected cases trio samples available. To comparison, two teams analysts alternatively allocated blinded each other's analysis. The time bioinformatics, analysis, diagnostic utility recorded evaluation. ES revealed five positive diagnoses (5/60, 8.3%) four made (4/30, 13%) during 2. Subsequently, diagnosis identified overall yield 10/61 (16.4%) reached. Among those clinical suspicion PCD (n = 31/61), 26% 8/31). While did not increase yield, we showed that variant uncertain significance could only detected due improved coverage over hence potential benefit future. We show essential component early-onset bronchiectasis most effective used combination tools TEM HSVM. Our vs. suggests are comparable diagnosis.