Identification of distinct ciliary beat pattern abnormalities by high-speed video microscopy in primary ciliary dyskinesia (original) (raw)

European Respiratory Journal, 2015

Abstract

Introduction: Primary Ciliary Dyskinesia (PCD) is a rare, genetically heterogenous disorder leading to recurrent respiratory tract infections due to abnormal ciliary motility causing impaired mucociliary clearance. High-speed videomicroscopy analysis (HVMA) of ciliary beat pattern (CBP) and frequency as the current first-line diagnostic tool is an increasing challenge, because current studies widely expended the spectrum of HVMA findings from very subtle to markedly abnormal. Objectives: We assigned typical HVMA findings to genetically confirmed PCD individuals in order to identify typical patterns for various PCD variants. Methods: We assessed 1072 videos from nasal brush biopsies of 66 PCD individuals by HVMA as part of routine diagnostic work-up. HVMA findings were subsequently correlated with the genotype (biallelic mutations in 17 genes). Results: Distinct CBP correlated well with genetic findings, which allows the classification of typical HVMA findings for various genetic groups: Respiratory cilia with outer dynein arm defects (ODA) showed minimal residual movements with a minority of cilia being completely immotile. Cilia with combined inner (IDA) and ODA defects were completely immotile. Defects of the central pair apparatus resulted in a rigid and uncoordinated CBP. Combined IDA and microtubular disorganization defects resulted in a hyperkinetic, very stiff and vibratory CBP. Nexin link defects showed an almost regular CBP with only slightly reduced beating amplitude. Conclusion: This study improves clinical PCD diagnostics by classifying different PCD subtypes using HVMA as the first-line diagnostic tool and facilitates the subsequent diagnostics.

Petra Pennekamp hasn't uploaded this paper.

Let Petra know you want this paper to be uploaded.

Ask for this paper to be uploaded.