{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNU4ATAC encodes U4atac, a small nuclear RNA that is an essential component of the minor (U12‐dependent) spliceosome responsible for the excision of a specialized subset of introns from pre‐messenger RNAs. Disruption of U4atac function compromises minor intron splicing, a process fundamental to normal gene expression and early human development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in RNU4ATAC have been identified in a spectrum of developmental disorders—including microcephalic osteodysplastic primordial dwarfism type I (MOPD I), Taybi‐Linder syndrome (TALS), Roifman syndrome, and Lowry Wood syndrome—demonstrating that altered U4atac impairs the splicing of U12‐dependent introns. Functional studies have shown that point mutations can either reduce U4atac expression or disrupt its ability to bind essential spliceosomal proteins, ultimately perturbing the formation of the U4atac/U6atac·U5 tri-snRNP complex and leading to widespread splicing defects that account for growth retardation, skeletal dysplasia, microcephaly, and even immune deficiencies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies underscore that RNU4ATAC is critical not only for the precise removal of minor introns but also for the maintenance of overall transcript integrity. Mutations affecting key structural domains—such as the 5′ and 3′ stem‐loops required for di-snRNP formation—can lead to a range of phenotypic manifestations, including recently characterized retinal abnormalities in Roifman syndrome, further highlighting the broad developmental consequences of impaired U4atac function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Huiling He, Sandya Liyanarachchi, Keiko Akagi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2011.01756.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2011.01756.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21815888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21815888"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ghada M H Abdel-Salam, Noriko Miyake, Maha M Eid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.34299"}], "href": "https://doi.org/10.1002/ajmg.a.34299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21990275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21990275"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Mahmoud Issa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.35356"}], "href": "https://doi.org/10.1002/ajmg.a.35356"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22581640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22581640"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Nihal A Hassan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Further delineation of the clinical spectrum in RNU4ATAC related microcephalic osteodysplastic primordial dwarfism type I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.36009"}], "href": "https://doi.org/10.1002/ajmg.a.36009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23794361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23794361"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Faegheh Jafarifar, Rosemary C Dietrich, James M Hiznay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical defects in minor spliceosome function in the developmental disorder MOPD I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.045187.114"}], "href": "https://doi.org/10.1261/rna.045187.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24865609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24865609"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Daniele Merico, Maian Roifman, Ulrich Braunschweig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9718"}], "href": "https://doi.org/10.1038/ncomms9718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26522830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26522830"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "A Putoux, A Alqahtani, L Pinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Refining the phenotypical and mutational spectrum of Taybi-Linder 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.12781"}], "href": "https://doi.org/10.1111/cge.12781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27040866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27040866"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Laura S Farach, Mary E Little, Angela L Duker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.38581"}], "href": "https://doi.org/10.1002/ajmg.a.38581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29265708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29265708"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ye Wang, Xueli Wu, Liu Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genomics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40246-018-0135-9"}], "href": "https://doi.org/10.1186/s40246-018-0135-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29370840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29370840"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jessica Heremans, Josselyn E Garcia-Perez, Ernest Turro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal differentiation of B cells and megakaryocytes in patients with Roifman syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2017.11.061"}], "href": "https://doi.org/10.1016/j.jaci.2017.11.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29391254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29391254"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ivan Shelihan, Sophie Ehresmann, Cinzia Magnani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-018-1950-8"}], "href": "https://doi.org/10.1007/s00439-018-1950-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30368667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30368667"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hugh J McMillan, Jorge Davila, Matt Osmond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole genome sequencing identifies pathogenic RNU4ATAC variants in a child with recurrent encephalitis, microcephaly, and normal stature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62457"}], "href": "https://doi.org/10.1002/ajmg.a.62457"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34405953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34405953"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Brian G Ballios, Amarilla Mandola, Alaa Tayyib, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deep phenotypic characterization of the retinal dystrophy in patients with RNU4ATAC-associated Roifman syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eye (Lond) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41433-023-02581-1"}], "href": "https://doi.org/10.1038/s41433-023-02581-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37225827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37225827"}]}]}]}