{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSNORD118 is the gene that encodes the U8 small nucleolar RNA (snoRNA), a specialized box C/D RNA integral to ribosome biogenesis. Unlike most snoRNAs that guide 2′-O-methylation, U8 is atypical in that it directs precise cleavage events during the maturation of precursor ribosomal RNAs, ultimately producing essential components of the large ribosomal subunit (5.8S and 28S rRNAs). This unique function ensures proper ribosome assembly and cellular protein synthesis, which is fundamental for cell viability and overall organismal homeostasis."}, {"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 SNORD118 have been robustly linked to the neurovascular disorder leukoencephalopathy with calcifications and cysts (LCC). Biallelic variants disrupt U8 expression, its processing, and its interaction with proteins, thereby impairing ribosome biogenesis and, ultimately, cerebral vascular homeostasis. Detailed molecular studies indicate that while some variants cause severely deleterious effects, many patients possess a mix of severe and milder mutations—often affecting the 3′-end processing of precursor-U8—that together determine the disease’s clinical spectrum. This genetic etiology clearly distinguishes LCC from phenotypically similar conditions such as Coats plus syndrome, where mutations in other genes like CTC1 are observed."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore the critical role of SNORD118 and its product, the U8 snoRNA, in ensuring efficient ribosome biogenesis—a function that is unexpectedly tied to the maintenance of neurovascular integrity. The pronounced variability in disease onset and severity among patients, including marked intrafamilial differences, highlights the complex genotype–phenotype correlations underlying LCC. This emerging understanding of SNORD118’s function not only provides insight into the mechanisms of ribosome maturation but also reveals how subtle alterations in a non-protein-coding RNA can precipitate devastating cerebral microangiopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emma M Jenkinson, Mathieu P Rodero, Paul R Kasher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3661"}], "href": "https://doi.org/10.1038/ng.3661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27571260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27571260"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Emily J McFadden, Susan J Baserga "}, {"type": "b", "children": [{"type": "t", "text": "U8 variants on the brain: a small nucleolar RNA and human disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2022.2048563"}], "href": "https://doi.org/10.1080/15476286.2022.2048563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35389826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35389826"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kazuhiro Iwama, Takeshi Mizuguchi, Jun-Ichi Takanashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.12991"}], "href": "https://doi.org/10.1111/cge.12991"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28177126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28177126"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "O Osman, P Labrune, P Reiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rev Neurol (Paris) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurol.2019.06.006"}], "href": "https://doi.org/10.1016/j.neurol.2019.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31521395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31521395"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yanick J Crow, Heather Marshall, Gillian I Rice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum."}]}, {"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.61907"}], "href": "https://doi.org/10.1002/ajmg.a.61907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33029936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33029936"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Patrick W Cullinane, Sally Ann Lynch, Michael Marnane "}, {"type": "b", "children": [{"type": "t", "text": "Phenotypic Variability in Leukoencephalopathy with Brain Calcifications and Cysts: Case Report of Siblings from an Irish Traveller Family with a Homozygous SNORD118 Mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-020-01550-7"}], "href": "https://doi.org/10.1007/s12031-020-01550-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32361877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32361877"}]}]}]}