The importance of genomic profiling for differential diagnosis of pediatric lung disease patients with suspected ciliopathies

Abstract

Introduction/Objective Dysfunction of the axonemal structure leads to ciliopathies. Sensory and motile ciliopathies have been associated with numerous pediatric diseases, including respiratory diseases. Primary ciliary dyskinesia (PCD) is ciliopathy linked to the dysfunction of motile cilia. Motile ciliary dysfunction in childhood leads to chronic rhinosinusitis, persistent cough, neonatal respiratory distress, bronchiectasis, and situs inversus (SI) have 50% of patients. These symptoms are common among pediatric lung diseases, which additionally makes it difficult to establish the accurate diagnosis. The aim of the study was to point out the significance of genomic profiling for patients with suspected ciliopathies and to design a strategy for genomic analysis relevant for differential diagnosis of lung disease patients with suspected ciliopathies. Methods We conducted a bioinformatic analysis of data generated by New Generation Sequencing (NGS) approach of 21 patients with final or suspected diagnosis of PCD. It was analyzed 93 genes: 29 PCD genes, 45 genes related to individual symptoms of lung diseases, and 19 genes related to sensory ciliopathies. Results The algorithm we have designed, enabled us to establish the clinical and genetic diagnosis for 17/21 (80.95%) patients, among which 11/21 (52.38%) were PCD patients. In 3/21 (14.28%) patients we detected monoallelic variants in PCD disease-causing genes. In 6/21 (28.57%) patients, variants in genes for other pulmonary diseases were detected, and for one patient, genetic background of disease remained unclear. Conclusion An improved strategy for easier and faster establishment of final diagnosis of ciliopathies is mandatory and includes both, clinical and genetic confirmation of disease.

Genetic basis of otosclerosis

“…It contributes to the discovery of new diseasecausing and disease-related genetic markers of complex rare diseases, which could be implemented in clinical practice [45]. Using NGS in families affected by otosclerosis, analyzing disease-affected and disease-nonaffected family members, sharing the same genetic background, can add to understanding the molecular basis of the disease [46]. However, due to its complex pathophysiology, otosclerosis is not a disease whose genetic base will be easily understood.…”