title: Genetics and biology of primary ciliary dyskinesia.
abstract: Ciliopathies are a growing class of disorders caused by abnormal ciliary axonemal structure and function. Our understanding of the complex genetic and functional phenotypes of these conditions has rapidly progressed. Primary ciliary dyskinesia (PCD) remains the sole genetic disorder of motile cilia dysfunction. However, unlike many Mendelian genetic disorders, PCD is not caused by mutations in a single gene or locus, but rather, autosomal recessive mutation in one of many genes that lead to a similar phenotype. The first reported PCD mutations, more than a decade ago, identified genes encoding known structural components of the ciliary axoneme. In recent years, mutations in genes encoding novel cytoplasmic and regulatory proteins have been discovered. These findings have provided new insights into the functions of the motile cilia, and a better understanding of motile cilia disease. Advances in genetic tools will soon allow more precise genetic testing, mandating that clinicians must understand the genetic basis of PCD. Here, we review genetic mutations, their biological impact on cilia structure and function, and the implication of emerging genetic diagnostic tools.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: horani_a@kids.wustl.edu.
authors.forename: Amjad
authors.initials: A
authors.lastname: Horani
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ferkol
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Dutcher
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
mesh_terms: D000818:Animals; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007619:Kartagener Syndrome / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: D005819:Genetic Markers
keywords: Cilia; Ciliogenesis; Genetic sequencing; Genetic testing; Primary ciliary dyskinesia; Rare lung disease