video: Toomer et al. found that primary cilia (green), which serve as cellular antennae to receive signals from the extracellular space (grey) are required for cardiac valve development. Blue stained are cell nuclei. This material relates to a paper that appeared in the May 22, 2019, issue of Science Translational Medicine, published by AAAS. The paper, by K. Toomer at Medical University of South Carolina in Charleston, SC; and colleagues was titled, 'Primary cilia defects causing mitral valve prolapse.' view more
Credit: Katelynn Toomer, Johns Hopkins postdoctoral Fellow; Russell Norris, Associate Professor of Medicine, the Medical University of South Carolina
Katelynn Toomer and colleagues have discovered that defects in tiny, hair-like cellular structures can lead to mitral valve prolapse (MVP), a common heart disorder that affects up to one in 40 people worldwide. Their findings - based on a genetic analysis of a multigenerational family with an inherited form of the disease - identify a potential underlying cause of this widespread but little-understood condition. MVP usually causes only mild symptoms in patients, but in some cases it can result in abnormal heart rhythm and loss of heart function. Despite the disease's prevalence, scientists do not yet fully understand why MVP occurs or how it unfolds in the heart. In this study, Toomer et al. tracked the development of human and mouse mitral valves and discovered that a loss of cilia - antenna-like structures that receive signals from outside a cell - in valve tissue caused congenital defects that mirrored those seen in patients with MVP. They also studied gene expression in a multigenerational family (43 members), 11 of whom had an inherited form of MVP, as well as data from a previous genetic study of 1,412 MVP cases. The analysis revealed that the patients with MVP harbored a mutation in a gene named DZIP1 that normally guides proper cilia growth. Further experiments showed that mouse pups lacking DZIP1 displayed impaired formation of cilia during their development, which was followed by MVP and valve defects later in life. The study's insights into the genetic and cellular origins of MVP could facilitate the design of drug-based interventions for the condition, which can currently only be treated with surgery.
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Journal
Science Translational Medicine