{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTTC21B encodes the intraflagellar transport protein IFT139, a critical component of the retrograde transport system within the primary cilium. This protein plays an essential role in the assembly, maintenance, and signaling of cilia, ensuring proper ciliary function and structure. Disruptions in TTC21B compromise these processes and are central to the pathogenesis of a broad range of ciliopathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPathogenic variants in TTC21B have been causally linked to an array of kidney disorders. Notably, mutations in this gene are associated with nephronophthisis‐related ciliopathies, Jeune asphyxiating thoracic dystrophy, and focal segmental glomerulosclerosis. In families carrying the recurrent p.P209L mutation, aberrant localization and function of IFT139 in podocytes lead to defects in primary cilia, abnormal cell migration, and cytoskeletal disruptions, collectively contributing to both glomerular and tubulointerstitial lesions. Furthermore, TTC21B mutations may act in trans with defects in other ciliary genes, highlighting their role as both causative and modifying alleles in the heterogeneous genetic landscape of renal ciliopathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its prominent role in renal disease, mutations in TTC21B contribute to a broader spectrum of ciliopathy features. Affected individuals may present with retinal dystrophy, skeletal malformations, biliary dysgenesis, and even heterotaxy, underscoring the multifaceted influence of IFT139 on diverse organ systems. These observations not only emphasize the critical role of TTC21B in ciliary biology but also reflect how allelic variation and gene–gene interactions can modulate phenotypic outcomes across ciliopathy disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Erica E Davis, Qi Zhang, Qin Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expanding the phenotype of CRB2 mutations - A new ciliopathy syndrome?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.12764"}], "href": "https://doi.org/10.1111/cge.12764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26925547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26925547"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gemma Bullich, Iván Vargas, Daniel Trujillano, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinical report and genetic analysis of rare premature infant nephronophthisis caused by biallelic TTC21B variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.2399"}], "href": "https://doi.org/10.1002/mgg3.2399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38439578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38439578"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Tamar Ben-Yosef, Nurit Asia Batsir, Tahleel Ali Nasser, et al. 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