CCDC114 is mutated in patient with a complex phenotype combining primary ciliary dyskinesia, sensorineural deafness,...

Ciliopathies-are widely recognized and associated with a wide variety of developmental and degenerative disorders. Most cilia-related diseases have renal manifestation, and there is a cross- overlapping relationship between gene mutations and cilia disease. Here, we investigated the clinical and pathological manifestation of a rare disease patient. We present the case of a 15-year-old child with dysplasia and multiple-organ damage who was initially diagnosed with nephrotic syndrome. The patient's kidney disease progressed to renal failure and received hemodialysis 10 months after renal biopsy. The individual presented primary ciliary dyskinesia (PCD) and additional symptoms including sensorineural deafness, kidney dysplasia, severe kidney function loss, and congenital heart disease which potentially linked to primary cilia deficiency. Cilia immunofluorescence of renal tissue showed a decrease in the number of cilium of the patient compared to the normal kidney. We identified a site mutation in CCDC114 (NM_144577 exon7 c. 596Cå T p. Ala199Val) by whole-exon sequences. We found that CCDC114 located at the basal body at cilia and the knockdown of CCDC114 could affect the occurrence of cilia in hRPE1 cells. The previous study of CCDC114 mainly lies in the motile cilia, and this study found that its impact on primary cilia thus broadened the understanding of overlapping function of different types of cilia.