Genetics and biology of primary ciliary dyskinesia - PubMed (original) (raw)

Review

Genetics and biology of primary ciliary dyskinesia

Amjad Horani et al. Paediatr Respir Rev. 2016 Mar.

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.

Keywords: Cilia; Ciliogenesis; Genetic sequencing; Genetic testing; Primary ciliary dyskinesia; Rare lung disease.

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Figures

Figure 1

Multiciliated cell differentiation. An airway epithelial progenitor cell, possessing a primary cilium, is directed toward the multiciliated cell type in a low Notch signaling condition. Under the influence of multiple transcription factors, hundreds of centrioles are generated, dock as basal bodies, and nucleate motile cilia in a step-wise process.

Figure 2

Ultrastructural defects associated with mutations in PCD-causative genes. Shown are cross sectional diagrams of a normal motile ciliary axoneme and those with specific ultrastructural defects that are observed in PCD.

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Genetics and biology of primary ciliary dyskinesia - PubMed (original) (raw)