Genotype-phenotype associations in Primary Ciliary Dyskinesia

​We examine possible associations between clinical phenotypes and genotypes in the inherited, primarily pulmonary disease Primary Ciliary Dyskinesia

​​​​​​A research project by Cand. Med. Mathias Geldermann Holgersen

Primary Ciliary Dyskinesia (PCD) is an innate, rare, primarily pulmonary disease with heterogeneous genetic origins. The pathology derives from dysfunctional cilia caused by abnormal structure and function, impairing mucociliary clearance. In healthy subjects, inhaled particles and pathogens are eliminated by upwards propulsion of mucus covering the respiratory tract mediated by coordinated ciliary motility. In PCD, abnormal function the mechanism leads to recurrent and often persistent suppurative respiratory infections causing inflammation and eventually structural and irreversible lung damage in a vicious cycle with gradually declining lung function.

More than 50 genes encode proteins responsible for normal functioning of cilia, and the reduced costs of genetic sequencing has resulted in an almost complete genotyping of the Danish PCD cohort.

Rigshospitalet serves as a nationwide PCD center, with 3-4 annual out-patient visits monitoring disease progression. This entails in an unprecedented amount of longitudinal data, leaving Denmark unique, even worldwide, as the long-term follow-up and data are far beyond what is available at other centers and previously reported.

In this project our overall aim is to utilize historic data and novel genotyping to explore possible associations of PCD genotypes and phenotypes including longitudinal markers of disease progression.

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