{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSki complex subunit 3 (SKIC3), encoded by TTC37 in humans and homologous to the yeast Ski3 protein, is an essential component of the cytoplasmic SKI complex that partners with the exosome to mediate 3′–5′ mRNA decay. Disruption of this process through mutations in TTC37 leads to impaired degradation of aberrant mRNAs, which is believed to contribute to the multisystem features observed in Tricho‐hepato‐enteric syndrome (THES), including intractable diarrhea, hair abnormalities, immunodeficiency, and, variably, liver disease. These mutations, spanning frameshift, splice-site, missense, and nonsense types, underscore the critical regulatory role of SKIC3 in maintaining mRNA quality control in diverse tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, clinical investigations have revealed that while both TTC37 (SKIC3) and SKIV2L are part of the human SKI complex, patients with SKIV2L deficiencies tend to manifest more severe liver involvement and prenatal growth impairment than those with TTC37 alterations. This differential impact further emphasizes the distinct yet cooperative roles played by each subunit within the SKI complex, which collectively ensure proper mRNA surveillance and decay."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional case reports have expanded the spectrum of TTC37 mutations and illustrate that, despite the genetic heterogeneity, the underlying molecular defect converges on a disturbed mRNA decay pathway. In some patients, truncating mutations in TTC37 (SKIC3) result in the production of a partially functional protein, suggesting that even a reduced role in the SKI complex can modulate the overall clinical presentation of THES."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexandre Fabre, Christine Martinez-Vinson, Bertrand Roquelaure, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in TTC37 associated with tricho-hepato-enteric syndrome."}]}, {"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.21420"}], "href": "https://doi.org/10.1002/humu.21420"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21120949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21120949"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexandre Fabre, Laetitia-Marie Petit, Lars F Hansen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new mutation in the C-terminal end of TTC37 leading to a mild form of syndromic diarrhea/tricho-hepato-enteric syndrome in seven patients from two families."}]}, {"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.38618"}], "href": "https://doi.org/10.1002/ajmg.a.38618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29383842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29383842"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Way Seah Lee, Kai Ming Teo, Ruey Terng Ng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in SKIV2L and TTC37 genes in Malaysian children with trichohepatoenteric syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.03.049"}], "href": "https://doi.org/10.1016/j.gene.2016.03.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27050310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27050310"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Patrice Bourgeois, Clothilde Esteve, Charlène Chaix, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tricho-Hepato-Enteric Syndrome mutation update: Mutations spectrum of TTC37 and SKIV2L, clinical analysis and future prospects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23418"}], "href": "https://doi.org/10.1002/humu.23418"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29527791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29527791"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sevil Dorum, Ozlem Gorukmez "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the clinical spectrum in trichohepatoenteric syndrome."}]}, {"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.62354"}], "href": "https://doi.org/10.1002/ajmg.a.62354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34037310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34037310"}]}]}]}