Primary ciliary dyskinesia and associated sensory ciliopathies

ABSTRACT

Primary ciliary dyskinesia (PCD) is a genetic disease of motile cilia, which belongs to a group of disorders resulting from dysfunction of cilia, collectively known as ciliopathies. Insights into the genetics and phenotypes of PCD have grown over the last decade, in part propagated by the discovery of a number of novel cilia-related genes. These genes encode proteins that segregate into structural axonemal, regulatory, as well as cytoplasmic assembly proteins. Our understanding of primary (sensory) cilia has also expanded, and an ever-growing list of diverse conditions has been linked to defective function and signaling of the sensory cilium. Recent multicenter clinical and genetic studies have uncovered the heterogeneity of motile and sensory ciliopathies, and in some cases, the overlap between these conditions. Here, we will describe the genetics and pathophysiology of ciliopathies in children, focusing on PCD, review emerging genotype-phenotype relationships, and diagnostic tools available for the clinician.

KEYWORDS:

• Primary ciliary dyskinesia
• bronchiectasis
• cilia
• basal body
• dynein

Declaration of interest

The authors were supported by the National Institutes of Health (NIH) grant, U54 HL09640958 and Children’s Discovery Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.