Determination of molecular etiology by using whole exome sequencing in patients affected by unclassified ciliopathies

Ciliopathies are a broad group of diseases that arise due to mutations in genes coding for proteins associated with cilia and centrosomes. The aim of this study is to elucidate the molecular etiology in patients with a suspicion of ciliopathy using next-generation sequencing and to expand the genotypic-phenotypic spectrum. The study was conducted at Hacettepe University, Department of Pediatrics, Department of Pediatric Genetic Diseases. Eight patients with a preliminary diagnosis of ciliopathy due to multiple anomalies, global developmental delay, dysmorphic features, or recurrent lung infections, were included in the study. Demographic characteristics, clinical history, laboratory and radiological findings were recorded. Whole exome sequencing was performed on DNA samples isolated from peripheral blood. The underlying molecular etiology was elucidated in five of the eight patients (62.5%). In the diagnosed group, causal variants were identified in BBS10, TTC26, CC2D2A, and CEP290 genes. Of the total 6 variants detected in these genes, 3 were novel variants. Previously unreported possible clinical associations were detected, such as tuba uterina atresia and the BBS10 gene variants, obesity and hemophagocytic syndrome and the CC2D2A gene variants. In the remaining three patients without a molecular diagnosis, no candidate variants were detected in two, while a candidate variant in the KRT71 gene was detected in one patient that could explain the hair findings. Our findings contribute to the expansion of the phenotypic and genotypic spectrum of ciliopathy group diseases.