Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.

Department of Cardiovascular Surgery 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Pathology Faculty of Medicine in Hradec Králové Charles University and Hospital Hradec Králové Hradec Králové Czechia

Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Pediatrics Faculty of Medicine in Hradec Králové Charles University and Hospital Hradec Králové Hradec Králové Czechia

Vera Vavrova Lab VIAL Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

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