Journal of Genetic Syndromes & Gene Therapy
Open Access

Abstract

Inner Dynein Arm Defects in Primary Ciliary Dyskinesia

A Shoemark, A Ives, A Becker-Heck, T Burgoyne, M Dixon, D Bilton, R Wilson, H Omran and C Hogg

Primary ciliary dyskinesia (PCD) is a genetic condition in which there is a defect in cilia motility. This can be caused by the absence of the inner dynein arm motor (IDA). The IDA can be difficult to observe by electron microscopy and has been shown to transiently disappear, making accurate diagnosis difficult. This study reviewed cases of PCD due to an IDA defect on the Royal Brompton Hospital database in order to confirm or retract the diagnosis. This was achieved using current methods of diagnosis (nasal nitric oxide, light and electron microscopy) and new techniques to improve visualisation of the IDA such as immunofluorescence analysis and 3D electron tomography. Four patients received normal results and the diagnosis of PCD was reversed. Three patients had another structural defect in combination with absence of IDAs. The remaining five patients had an absence of IDA in mean (SD) 42(22) % of their cilia. In these group diagnostic findings were heterogeneous with a diverse range of cilia beat pattern and frequencies. Immunofluorescent antibodies revealed the presence of the IDA component protein DNALI1 in all patients and high resolution electron tomography confirmed the presence of some IDA structures. Nasal nitric oxide values ranged from 3 to 463 ppb. In conclusion, PCD due to an IDA defect is difficult to diagnose as the IDA appears transiently absent on TEM. Diagnosis is reversed by repeat sampling in 38% patients. We suggest an isolated absence of IDA shown by TEM is not sufficient to confirm a diagnosis of PCD.