{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GSC2 (also referred to as GSCL or Gscl) is a homeobox‐containing transcription factor encoded within the 22q11 region. Multiple studies have identified and characterized this gene as a candidate for contributing to developmental disorders such as velocardiofacial syndrome/DiGeorge syndrome and oculo‐auriculo‐vertebral spectrum, suggesting that altered dosage in a multigenic context may underlie parts of their complex phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Expression analyses in both human and mouse models have revealed that GSC2/GSCL is expressed in a restricted pattern—most notably in specific brain regions (including the pons and interpeduncular nucleus) and in primordial germ cells—implying a role in neurodevelopment and even sleep regulation, as deficiency in mouse models leads to alterations in REM sleep architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although initial expectations posited that haploinsufficiency for GSC2 might directly account for many of the developmental defects observed in these syndromes, knockout and deletion studies indicate that loss of GSC2 alone does not recapitulate the full spectrum of the syndrome phenotypes. Instead, its functions appear to be integrated within a network of 22q11 genes, reinforcing the idea that complex multigenic interactions are at play."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, preliminary evidence from protein–protein interaction studies (via yeast two‐hybrid approaches) suggests that GSC2 may engage with regulatory factors—potentially contributing to autoregulatory loops or modulating nucleocytoplasmic trafficking—to fine‐tune transcriptional programs during early embryogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings support a model in which GSC2 functions as a region‐specific transcriptional regulator during early neural and gonadal development. Its localized expression and interactions with other critical developmental genes underscore its putative role in establishing proper craniofacial and neuronal structures as well as in modulating behaviors such as sleep. However, rather than acting alone, GSC2 likely contributes to the broader pathogenic mechanisms of 22q11–related syndromes through coordinated activity with other genes in the region.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C Albert Yeung "}, {"type": "b", "children": [{"type": "t", "text": "Effect of implant rehabilitation on oral health-related quality of life with three different implant strategies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Evid Based Dent (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41432-020-0112-8"}], "href": "https://doi.org/10.1038/s41432-020-0112-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32978537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32978537"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "N Galili, H S Baldwin, J Lund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A region of mouse chromosome 16 is syntenic to the DiGeorge, velocardiofacial syndrome minimal critical region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (1997)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.7.1.17"}], "href": "https://doi.org/10.1101/gr.7.1.17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9037598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9037598"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "S Gottlieb, B S Emanuel, D A Driscoll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (1997)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9150167"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9150167"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "B Funke, B Saint-Jore, A Puech, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and mutation analysis of goosecoid-like (GSCL), a homeodomain-containing gene that maps to the critical region for VCFS/DGS on 22q11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (1997)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/geno.1997.5046"}], "href": "https://doi.org/10.1006/geno.1997.5046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9441739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9441739"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hiromasa Funato, Makito Sato, Christopher M Sinton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1012764107"}], "href": "https://doi.org/10.1073/pnas.1012764107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20921407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20921407"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M Wakamiya, E A Lindsay, J A Rivera-Pérez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of Gscl in the pathogenesis of the DiGeorge and velocardiofacial syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/7.12.1835"}], "href": "https://doi.org/10.1093/hmg/7.12.1835"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9811926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9811926"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "B Saint-Jore, A Puech, J Heyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/7.12.1841"}], "href": "https://doi.org/10.1093/hmg/7.12.1841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9811927"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9811927"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "N Galili, S Nayak, J A Epstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rnf4, a RING protein expressed in the developing nervous and reproductive systems, interacts with Gscl, a gene within the DiGeorge critical region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/(SICI)1097-0177(200005)218:1"}, {"type": "a", "children": [{"type": "t", "text": "102::AID-DVDY9"}], "href": "102::AID-DVDY9"}, {"type": "t", "text": "3.0.CO;2-A"}], "href": "https://doi.org/10.1002/(SICI"}, {"type": "t", "text": "1097-0177(200005)218:1"}, {"type": "a", "children": [{"type": "t", "text": "102::AID-DVDY9"}], "href": "102::AID-DVDY9"}, {"type": "t", "text": "3.0.CO;2-A) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10822263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10822263"}]}]}]}