Ciliary phenotyping in renal epithelial cells in a cranioectodermal dysplasia patient with WDR35 variants

• DOI: 10.3389/fmolb.2023.1285790
• Publication Date: 2023-12-12T15:17:07Z
• Authors: Joanna Walczak-Sz...; Anna Wawrocka; Łukasz Kuszel; Paulina Pietras; Marta Leśniczak-S...; Mirosław Andrusie...; Maciej R. Krawczy...; Anna Latos-Bieleńska; Marta Pawlak; Ryszard Grenda; Anna Materna-Kiryluk; Machteld M. Oud; Witold Szaflarski
• Keywords: Ciliopathy; Ciliogenesis; Ciliopathies; Motile cilium; Genodermatosis; Intraflagellar Transport; Nephronophthisis

Background: Cranioectodermal dysplasia (CED) is a skeletal autosomal recessive ciliopathy. The characteristic clinical features of CED are facial dysmorphisms, short limbs, narrow thorax, brachydactyly, ectodermal abnormalities, and renal insufficiency. Thus far, variants in six genes known to be associated with this disorder: WDR35 , IFT122 IFT140 IFT144 IFT52 IFT43 . Objective: goal study was perform cilium phenotyping human urine-derived epithelial cells (hURECs) from patient diagnosed second-stage chronic kidney disease (CKD) three unrelated unaffected pediatric controls. Methods: Genetic analysis by screening performed the affected individual. Cilium frequency morphology, including length, height, width, were evaluated immunofluorescence (IF) experiments hURECs using two markers visualizing ciliary axoneme (Acet-Tub ARL13B) base (PCNT). IF results analyzed confocal microscope IMARIS software. Results: revealed presence nonsense p. (Leu641*) variant novel missense (Ala1027Thr). Moreover, comparative genomic hybridization showed that carries microdeletion on chromosome 7q31.1. Ciliary morphological differences patient’s cilia as compared significantly wider longer. Conclusion: obtained suggest CED-related CKD might identified harboring This points out added value functional testing for ciliopathies.