{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPCARE (previously designated C2ORF71) is a retina‐specific gene that plays a critical role in photoreceptor cell integrity and visual function. Multiple studies have demonstrated that PCARE is predominantly expressed in the retina, with localization to the primary cilium or connecting cilium of photoreceptor cells. Disruptive mutations—including truncating and missense variants—have been identified in patients with autosomal‐recessive retinitis pigmentosa, a disorder characterized by night blindness, constricted visual fields, and markedly diminished electroretinographic responses. Functional models, including early‐expression studies in the developing mouse eye and zebrafish knockdown experiments, confirm that PCARE is essential for the normal development and maintenance of photoreceptors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\nIn the broader context of inherited retinal degenerations, PCARE’s involvement is set against a complex backdrop of genetic heterogeneity that also encompasses syndromic forms such as Usher syndrome. Investigations integrating genome‐wide mapping and phenotypic characterization reinforce its role as a key factor in retinal dystrophy, while reviews of retinitis pigmentosa emphasize the interplay of multiple genetic loci that modulate photoreceptor viability and disease expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n\nEmerging studies have begun to explore potential extra‐retinal associations and the wider regulatory milieu in which PCARE operates. For example, researchers have evaluated genetic variants at the C2orf71 locus for possible links with colorectal cancer susceptibility, hinting at pleiotropic effects that may extend beyond visual physiology. Moreover, investigations into the translational control of retinal proteins and studies of related regulatory networks in other cellular systems—such as those governing dendritic cell apoptosis and m6A‐mediated mRNA translation—offer valuable context to the complex cellular pathways that underpin retinal health."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rob W J Collin, Christine Safieh, Karin W Littink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.03.016"}], "href": "https://doi.org/10.1016/j.ajhg.2010.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20398884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20398884"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Darryl Y Nishimura, Lisa M Baye, Rahat Perveen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.03.005"}], "href": "https://doi.org/10.1016/j.ajhg.2010.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20398886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20398886"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Panagiotis I Sergouniotis, Zheng Li, Donna S Mackay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A survey of DNA variation of C2ORF71 in probands with progressive autosomal recessive retinal degeneration and controls."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.10-6043"}], "href": "https://doi.org/10.1167/iovs.10-6043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20811058"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20811058"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Isabelle Audo, Marie-Elise Lancelot, Saddek Mohand-Saïd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel C2orf71 mutations account for ∼1% of cases in a large French arRP cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21460"}], "href": "https://doi.org/10.1002/humu.21460"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21412943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21412943"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christina Gerth-Kahlert, Amit Tiwari, James V M Hanson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C2orf71 Mutations as a Frequent Cause of Autosomal-Recessive Retinitis Pigmentosa: Clinical Analysis and Presentation of 8 Novel Mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.17-21597"}], "href": "https://doi.org/10.1167/iovs.17-21597"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28763557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28763557"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Samer Khateb, Lina Zelinger, Liliana Mizrahi-Meissonnier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2014-102287"}], "href": "https://doi.org/10.1136/jmedgenet-2014-102287"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24780881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24780881"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yangfan P Liu, Daniëlle G M Bosch, Anna M Siemiatkowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Putative digenic inheritance of heterozygous RP1L1 and C2orf71 null mutations in syndromic retinal dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/13816810.2016.1151898"}], "href": "https://doi.org/10.3109/13816810.2016.1151898"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27029556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27029556"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Markus Zwick, Thomas Ulas, Yi-Li Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the Phosphatase Ppef2 Controls Survival and Function of CD8"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Dendritic Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2019.00222"}], "href": "https://doi.org/10.3389/fimmu.2019.00222"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30809231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30809231"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shaofeng Jiang, Ying He, Rongrong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of chromosome 2 open reading frame 71 in colorectal cancer susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10147-022-02270-1"}], "href": "https://doi.org/10.1007/s10147-022-02270-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36396885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36396885"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yeming Yang, Xiaoyan Jiang, Junyao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The m[6]A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Genet Genomics (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jgg.2023.12.007"}], "href": "https://doi.org/10.1016/j.jgg.2023.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38157933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38157933"}]}]}]}