Abstract
BackgroundPrimary ciliary dyskinesia (PCD) is a rare disorder with variable disease progression. To date, mutations in more than 20 different genes have been found. At present, PCD subtypes are described according to the ultrastructural defect on transmission electron microscopy (TEM) of the motile cilia. PCD with normal ultrastructure (NU) is rarely reported because it requires additional testing. Biallelic mutations in DNAH11 have been described as one cause of PCD with NU.The aim of our study was to describe the clinical characteristics of a large population of patients with PCD, in relation to the ultrastructural defect. Additionally, we aimed to demonstrate the need for biopsy and cell culture to reliably diagnose PCD, especially the NU subtype.MethodsWe retrospectively analyzed data from 206 patients with PCD. We compared the clinical characteristics, lung function, microbiology and imaging results of 68 patients with PCD and NU to those of 90 patients with dynein deficiencies and 41 patients with central pair abnormalities. In addition, we aimed to demonstrate the robustness of the diagnosis of the NU subtype in cell culture by data from genetic analysis.ResultsPCD with NU comprised 33% (68/206) of all patients with PCD. Compared to other subtypes, patients with PCD and NU had a similar frequency of upper and lower respiratory tract problems, as well as similar lung function and imaging. With the currently widely applied approach, without cell culture, the diagnosis would have been missed in 16% (11/68) of patients with NU. Genetic analysis was performed in 29/68 patients with PCD and NU, and biallelic mutations were found in 79% (23/29) of tested patients.ConclusionsWe reported on the clinical characteristics of a large population of patients with PCD and NU. We have shown that systematic performance of biopsy and cell culture increases sensitivity to detect PCD, especially the subtype with NU.PCD with NU has similar clinical characteristics as other PCD types and requires biopsy plus ciliogenesis in culture for optimal diagnostic yield.
Highlights
Primary ciliary dyskinesia (PCD) is a rare disorder with variable disease progression
Between January 1990 and August 2012, PCD was diagnosed in 206 patients
Ninety patients were diagnosed with PCD with dynein deficiencies (DD) (44%)(45 outer dynein arm (ODA) deficiency, 37 partial ODA deficiency and 8 inner dynein arm (IDA) and ODA deficiency)
Summary
Primary ciliary dyskinesia (PCD) is a rare disorder with variable disease progression. PCD subtypes are described according to the ultrastructural defect on transmission electron microscopy (TEM) of the motile cilia. Primary ciliary dyskinesia (PCD) is a rare disease [1], caused by congenital abnormalities in both structure and function of the motile cilia. It is characterized by upper and lower respiratory tract infections, an increased incidence of situs inversus (SI) and male infertility. Specific genes are linked to distinct ciliary ultrastructural abnormalities on transmission electron microscopy (TEM): mutations in DNAI1, DNAH5, TXNDC3, DNAI2, DNAL1, CCDC114 and ARMC4 cause PCD with outer dynein arm (ODA) deficiency [2,3,4], whereas mutations in DNAAF1, DNAAF2, DNAAF3, HEATR2, LRRC6, CCDC103, DYX1C1, ZMYND10, SPAG1 and C21orf cause combined inner dynein arm (IDA) and ODA deficiency [2,5,6,7,8]. DNAH11 mutations are rare in population studies [16] and the frequency of PCD with NU remains under discussion
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