Primary ciliary dyskinesia (PCD): A genetic disorder of motile cilia

Abstract

Primary ciliary dyskinesia (PCD) is a genetic disorder of motile cilia. Clinical features include chronic oto-sinopulmonary disease, laterality defects, and male fertility reflecting impaired function of respiratory cilia in the upper and lower respiratory tracts, nodal cilia in the embryonic node and sperm tails, respectively. Recent studies have identified over 40 PCD-associated genes that encode proteins involved in ciliary biogenesis, assembly, structure, or function. Mutations in these genes account for approximately 70% of PCD cases; therefore, further gene discovery is expected. The diagnosis of PCD is challenging because no single test has the required diagnostic accuracy. Recent efforts have focused on standardizing and validating a panel of tests (including assessment for key clinical features, nasal nitric oxide measurement, ciliary ultrastructure analysis, and PCD genetic testing) to be used at PCD Centers to accurately diagnose PCD. Multi-center research programs focused on PCD in North America and Europe have been crucial for PCD gene discovery, advancing our understanding of the natural history of PCD and launching multi-center clinical trials.

Primary ciliary dyskinesia and psychological well-being in adolescence

“…It is characterized by chronic upper and lower respiratory tract infections, including the middle ear, from birth [4,5]. Bronchiectasis is present in more than 80% of patients [6], leading to recurrent and chronic lung damage. The involvement of scourges of both male and female reproductive cells is what predisposes patients to infertility, a characteristic feature of this pathology [6].…”

“…Bronchiectasis is present in more than 80% of patients [6], leading to recurrent and chronic lung damage. The involvement of scourges of both male and female reproductive cells is what predisposes patients to infertility, a characteristic feature of this pathology [6]. Studies indicate that 1/15,000-20,000 live births [7] will present the disease, with a similar distribution among boys and girls [2,8].…”

“…Despite medical advances, there is currently no treatment to correct ciliary dysfunction in PCD. Most treatments applied to patients with PCD are similar to those used with other similar diseases, such as cystic fibrosis [1,6,9].…”

Rare Human Diseases: Model Organisms in Deciphering the Molecular Basis of Primary Ciliary Dyskinesia

“…Until now, mutations in more than 40 genes have been shown to cause PCD. However, it is estimated that the genes identified to date account for only 60-70% of all PCD cases [25].…”

“…The elucidation of this puzzle has led to the discovery of (1) the cytoplasmic proteins (called dynein axonemal assembly factors, DNAAFs) that act as co-chaperons during the preassembly of the dynein arms, and (2) proteins that play a role in the preassembly and/or transport of ODAs and IDAs to cilia. To date, mutations in the following genes were shown to cause PCD with ultrastructural changes described above: DNAAF1/LRRC50 (leucine-rich repeat containing) [MIM: 613190] [ [148]; for review, see [25].…”