Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency

Author:

Kronquist Elise K.,Kaur Maninder,Gober Leah M.,Knutsen Russell H.ORCID,Fu Yi-Ping,Yu Zu-XiORCID,Donahue Danielle R.,Chen Marcus Y.,Osgood Sharon,Raja Neelam,Levin Mark D.,Barochia Amisha,Kozel Beth A.

Abstract

Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (ELN), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18–55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in Eln+/− and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) were lower in adults with WS (p < 0.0001 and p < 0.05, respectively). The FEV1/FVC ratio was more frequently below the lower limit of normal in cases (p < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (p < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (p < 0.0001). In Eln+/− mice, ex vivo lung volumes were increased (p < 0.0001), with larger airspaces (p < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS.

Funder

National Institutes of Health

Publisher

MDPI AG

Subject

Clinical Biochemistry

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Occurrence of Emphysema in Individuals With Williams-Beuren Syndrome;CHEST Pulmonary;2024-05

2. Emerging mechanisms of elastin transcriptional regulation;American Journal of Physiology-Cell Physiology;2022-09-01

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