The evolving spectrum of ciliopathies and respiratory disease

Abstract

Purpose of review Research on the biology of cilia, complex hair-like cellular organelles, has greatly informed our understanding of its crucial role in respiratory health and the pathogenesis of Primary Ciliary Dyskinesia (PCD), including the genetics behind this condition. This review will summarize the current state of the art in the field highlighting its clinical implications. Recent findings The genetics of PCD have exploded over the past few years as knowledge acquired from model systems has permitted the identification of genes that are key components of the ciliary apparatus and its function. In addition clinical criteria and diagnostic tools have emerged that are permitting more clear identification of affected individuals. Summary The rate of progress in the field continues to accelerate through international collaborative efforts and standardization of methods. Although the genetics behind PCD are complex given the large number of genes associated with disease as well as the large number of possible mutations even at the individual gene level, this knowledge is rapidly translating in improved diagnostics and hopefully in the near future in the identification of potential therapeutics.

C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia

“…1 Motile and non-motile types of cilia in the human body have differences in their axoneme structural arrangement and motilities. 2,3 Non-motile primary cilia present on most cells contain nine pairs of microtubules forming a circular scaffold of nine-fold symmetry termed 9þ0. Nodal cilia of the embryonic left-right organizer (node) have a similar structure but with dynein ''arm'' motor subunits attached to the peripheral microtubules that provide motility machinery for ciliary beating.…”

Airway Epithelial Cell Cilia and Obstructive Lung Disease

“…Additionally, links between genetics and ciliary function and structure are demonstrated in several studies [30,31,32,33]. For information on the relationship between genes and cilia structure and function, we refer the readers to recent extensive reviews on this subject [1,3,15,31,34,35]. Another important factor in the function of cilia is the mucus layer composition and thickness [36,37,38].…”

CEP97 phosphorylation by Dyrk1a is critical for centriole separation during multiciliogenesis

“…The Dyrk1a gene maps in the Down syndrome critical region, and recurrent respiratory infections are observed in patients ( Santoro et al, 2021 ), suggesting the possibility that deregulated Dyrk1a expression may have an impact on multiciliogenesis and/or cilia function in the respiratory tract. In fact, respiratory tract infections are common in many patients with ciliopathy ( Milla, 2016 ). Our findings on the collaborative role of CEP97 and Dyrk1a in multiciliation may add to our existing knowledge regarding pericentrin overexpression in patients with trisomy 21 and therapeutic approaches for the respiratory diseases in patients with ciliopathy and Down syndrome.…”