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Background: Primary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages. The conditional reprogramming culture (CRC) method, a combination of a Rho-kinase inhibitor and fibroblast feeder cells, has been applied to cystic fibrosis. The goal of this study was to evaluate the value of CRC in diagnosing PCD in Japanese patients.
Methods: Eleven patients clinically suspected of having PCD were included. Airway epithelial cells were obtained from an endobronchial forceps biopsy and cultured at the air-liquid interface (ALI) combined with CRC. Ciliary movement, ultrastructure, and mutated ciliary protein evaluation were performed using HSVA, TEM, and IF, respectively. Genetic testing was performed on some patients.
Results: CRC yielded dense and well-differentiated ciliated cells with a high success rate (∼90%). In patients with PCD, the ciliary ultrastructure phenotype (outer dynein arm defects or normal ultrastructure) and IF findings (absence of the mutated ciliary protein) were confirmed after CRC. In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis.
Conclusions: CRC could be a potential tool for improving diagnostic accuracy and contributing to future clinical and basic research in PCD.
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http://dx.doi.org/10.1016/j.resinv.2022.02.003 | DOI Listing |
Ann Am Thorac Soc
December 2024
The Hospital for Sick Children, Division of Respiratory Medicine, Translational Medicine, Research Institute, Toronto, Ontario, Canada.
Rationale: Patients with Primary Ciliary Dyskinesia (PCD) experience acute pulmonary exacerbations (PEx). In Cystic Fibrosis (CF), PEx treated with oral antibiotics (oPEx) were found to be related to short and long-term lung function deficits, however the impact oPEx on lung function in patients with PCD has not yet been assessed.
Objective: To assess the impact of oPEx on lung function recovery in PCD and determine the factors associated with poorer response.
ERJ Open Res
November 2024
Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Hôpital Bicêtre, Service d'ORL, Le Kremlin-Bicêtre, France.
Background: Recurrent infections of the nose, sinuses and ears are common problems for people with primary ciliary dyskinesia. While pulmonary exacerbations in primary ciliary dyskinesia are defined, there is no definition for ear-nose-throat exacerbations, a potential outcome for research and clinical trials.
Methods: We set up an expert panel of 24 ear-nose-throat specialists, respiratory physicians, other healthcare professionals and patients to develop consensus definitions of sinonasal and otological exacerbations in children and adults with primary ciliary dyskinesia for research settings.
Basic Clin Androl
December 2024
RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic.
Background: Primary ciliary dyskinesia (PCD) is a heterogenous disease caused by mutations of miscellaneous genes which physiologically play an important role in proper structure and/or function of various cellular cilia including sperm flagella. Besides male infertility, the typical phenotypes, based on decreased mucociliary clearance, are lifelong respiratory issues, i.e.
View Article and Find Full Text PDFJ Hum Genet
December 2024
John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Sex chromosome aneuploidies (SCA) such as Turner, Klinefelter, Jacobs, and Trisomy X syndromes are prevalent genetic disorders with well-established phenotypes. Challenges persist, however, in determining the need for further genetic evaluation in cases of affected individuals exhibiting atypical symptoms. The present study retrospectively examined 54 pediatric patients with an SCA diagnosis at a single institution between January 2015 and December 2023.
View Article and Find Full Text PDFEur Respir J
December 2024
Departments of Medicine and Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.
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