TY - JOUR
T1 - Genetics and biology of primary ciliary dyskinesia
AU - Horani, Amjad
AU - Ferkol, Thomas W.
AU - Dutcher, Susan K.
AU - Brody, Steven L.
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Cilia
KW - Ciliogenesis
KW - Genetic sequencing
KW - Genetic testing
KW - Primary ciliary dyskinesia
KW - Rare lung disease
UR - http://www.scopus.com/inward/record.url?scp=84951856817&partnerID=8YFLogxK
U2 - 10.1016/j.prrv.2015.09.001
DO - 10.1016/j.prrv.2015.09.001
M3 - Review article
C2 - 26476603
AN - SCOPUS:84951856817
SN - 1526-0542
VL - 18
SP - 18
EP - 24
JO - Paediatric Respiratory Reviews
JF - Paediatric Respiratory Reviews
ER -