{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CPLANE1—previously known as C5orf42 and also referred to as JBTS17—is emerging as a multifunctional protein that plays key roles in ciliogenesis and neural development. Several recent studies demonstrate that CPLANE1 localizes to the ciliary transition zone where it is critical for the proper formation and function of primary cilia, acting upstream of other transition zone proteins such as NPHP1 and CEP290."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In both human patients and animal models, mutations in CPLANE1 underlie a spectrum of ciliopathies—including Joubert syndrome and oral‐facial‐digital syndrome type VI—characterized by distinctive neuroimaging features, mid‐hindbrain malformations, and variable extracerebral defects. Notably, the lack of a simple genotype–phenotype correlation argues that additional genetic modifiers contribute to the overall expressivity of CPLANE1‐related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, beyond its established role in ciliogenesis, recent evidence indicates that CPLANE1 may also have extraciliary functions. Investigations using RNA interference and in vivo electroporation strategies in developing mouse cortex reveal that CPLANE1 localizes to the kinetochore and is involved in the regulation of mitotic progression. Deficiency of CPLANE1 disrupts proper chromosome alignment and spindle orientation by affecting the localization of key mitotic regulators such as LIS1, providing a putative mechanistic link between abnormal ciliary function and cortical malformation phenotypes like microcephaly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that CPLANE1 is indispensable for the establishment and maintenance of the primary cilium—a sensory and signaling hub—and is also necessary for ensuring accurate mitosis during neurogenesis. The pleiotropic consequences of CPLANE1 mutations highlight its dual role in ciliary structure/function and cell division, which together contribute to the broad clinical spectrum observed in ciliopathy patients.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rama Rao Damerla, Cheng Cui, George C Gabriel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Jbts17 mutant mouse model of Joubert syndrome with cilia transition zone defects and cerebellar and other ciliopathy related anomalies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv137"}], "href": "https://doi.org/10.1093/hmg/ddv137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25877302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25877302"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carine Bonnard, Mohammad Shboul, Seyed Hassan Tonekaboni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in the ciliopathy-associated gene CPLANE1 (C5orf42) cause OFD syndrome type VI rather than Joubert syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2018.03.012"}], "href": "https://doi.org/10.1016/j.ejmg.2018.03.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29605658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29605658"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qiuyan Liu, Haiqiao Wang, Jianhui Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Four novel compound heterozygous mutations in C5orf42 gene in patients with pure and mild Joubert syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Dev Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jdn.10029"}], "href": "https://doi.org/10.1002/jdn.10029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32233090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32233090"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hyowon Hong, Kwangsic Joo, Sang Min Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extraciliary roles of the ciliopathy protein JBTS17 in mitosis and neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.25491"}], "href": "https://doi.org/10.1002/ana.25491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31004438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31004438"}]}]}]}