40 also associated with situs inversus—a mirror image arrangement of the internal body organs (Kartagener’s syndrome [KS]) (Afzelius 1998). The respiratory symp- toms, which are the primary cause for PCD patients’ presentation to the physician, reflect the impairment of mucociliary clearance caused by the dysfunction of motile cilia in the respiratory epithelium (RE). Subfertility in PCD patients is due to the dysfunction of flagella in spermatozoa and of cilia in the epithelium lining of the oviducts. Randomization of the organ symmetry in KS is caused by the impaired motility of the cilia present in the embryonic node, during the early phase of development (Geremek and Witt 2004). Proper diagnosis of PCD, especially in patients without situs inversus, is often impeded by the fact that aberrant ciliary function (with clinical manifestation similar to PCD) can also result from non-hereditary mucosal injuries, due to inflammation, bacterial or viral infections, allergies, and smoking (Escudier et al. 2009). Such acquired cilia alterations are transient and collectively named secondary ciliary dyskinesia (SCD) (Jorissen et al. 1997). Clinically, SCD symptoms are similar or even indistinguishable from those of PCD; furthermore, PCD-caused inflammation leads to further, secondary changes of the ciliary function. This superimposition of the genetic and environmental defects can heavily perturb and obstruct the differential diagnosis of PCD versus SCD. In the majority of cases, the inherited dysfunction of cilia in PCD is caused by aberrations in the ultrastructure of these organelles. A large diversity of ultrastructural defects reflects the complicated architecture of the cilium (Fig. 1). J Appl Genetics (2011) 52:39–51 Ultrastructural and functional defects in PCD Ultrastructural defects of the ciliary architecture can be identified by transmission electron microscopy (TEM). The most frequently observed defects (70–80%) involve the lack or shortening of outer (ODA) and/or inner (IDA) dynein arms (Noone et al. 2004) (Fig. 1, Table 1). Aberrant number and/or localization of the central or peripheral microtubules (MTs) form the other major class of ciliary defects (Table 1). While several different aberrations can be found in a single patient, the defects are often not present in all of the examined cilia; furthermore, some patients do not have any recognizable ultrastructural defects at all (Jorissen et al. 1997; Herzon and Murphy 1980; Greenstone et al. 1983; Escudier et al. 2009; Conraads et al. 1992). It is important to realize that not all of the structural changes observed in TEM represent generic defects. Some of them may result from the inappropriate preparation of a specimen (for example, dynein arms, especially IDA, are hard to observe in TEM specimens of low quality). Other changes, like the absence of a central MT pair, may not reflect any abnormality, but just the normal architecture of the proximal part of the cilium (at the level of the transition zone), where the central pair is not present (Fig. 1). What is more, abnormal- ities of the ciliary ultrastructure are not solely restricted to PCD patients. MT defects or swollen cilia are frequently found in patients with different respiratory-tract pathologies (such as cystic fibrosis, bronchial asthma, and bronchitis) (Afzelius 1981). Similarly, discordant orientation of neigh- boring cilia can occur not only as a primary (genetic) defect, but also secondary to an infection (Rutland and de Iongh 1990). In addition, even in non-PCD individuals, up to 10% Fig. 1 Schematic representation of the ciliary architecture. a Arrangement of microtubules (MTs) in different sections of the cilium. The main body of the organelle, the axoneme, is built of nine peripheral microtubular doublets, organized symmetrically around the central pair of MTs. The arrangement of MTs is different in the proximal parts of the cilium, with the central pair missing in the transition zone and in the anchoring basal body (kinetosome); in addition, in the basal body, peripheral MT doublets are replaced with triplets. b MTs and associated elements in the section of axoneme. Axonemal MTs are associated with a variety of proteins, which form specific elements of the ciliary ultrastructure, periodically arranged along the axoneme length. Dynein arms, outer (ODA) and inner (IDA), are composed of several types of axonemal dynein chains— light, intermediate, and heavy. The heavy dynein chains act as ATP- dependent molecular motor complexes, which generate the ciliary movement. Nexin bridges and radial spokes, each composed of a large number of different protein chains, connect the neighboring peripheral doublets to the central MT pair, stabilizing the ciliary ultrastructure