EOGT

Inheritance Pattern: AR

Disease ID:MONDO:0014124

Submitter: Labcorp Genetics (formerly Invitae)

Inheritance Pattern: AR

Disease ID:MONDO:0014124

Submitter: G2P

Inheritance Pattern: AR

Disease ID:MONDO:0014124

Submitter: Ambry Genetics

Inheritance Pattern: AD

Disease ID:MONDO:0007034

Submitter: Orphanet

Inheritance Pattern: AR

Disease ID:MONDO:0014124

Submitter: PanelApp Australia

Inheritance Pattern: AR

Disease ID:MONDO:0014124

Submitter: ClinGen

*EOGT* was first reported in relation to Adams-Oliver syndrome, an autosomal recessive disorder, in 2013 (Shaheen et al, PMID: 23522784). Adams-Oliver syndrome is characterized by aplasia cutis congenita (ACC), typically affecting the vertex of the scalp, with underlying skull defects in more severe cases; transverse terminal limb defects; cutaneous vascular abnormalities such as cutis marmorata telangiectatica congenita; and, in some cases, congenital heart defects, vascular anomalies, growth impairment, and, less commonly, developmental delay or neurological abnormalities. *EOGT* encodes EGF domain-specific O-linked N-acetylglucosamine (O-GlcNAc) transferase which, in the ER, catalyzes the addition of a single O-GlcNAc residue to specific serine or threonine residues EGF-like repeats of secreted and cell-surface proteins such as NOTCH1 and other Notch receptors. Variants in EOGT have been implicated in only one condition, Adamas-Oliver syndrome 4. Ten variants (5 missense, 3 splice site, 2 frameshift) that have been reported in ten probands in six publications (Shaheen et al, 2013, PMID: 23522784; Cohen et al, 2014; PMID: 23860037; Meester et al, 2018, PMID: 29924900; Schröder et al, 2019, PMID: 31368252; Dudoignon et al, 2020, PMID: 31654484; He et al, 2026, PMID: 41959640) are included in this curation. Segregation evidence from three distantly-related families in the Bedouin population, which led to the identification of a founder frameshift variant, c.1074delA (p.Gly359AspfsTer28), was included (Cohen et al, 2014; PMID: 23860037). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by experimental evidence. *EOGT* was first identified as a novel OGT in Drosophila that O-GlcNAcylated the EGF repeats of Notch and Dumpy (Matsuura et al, 2008, PMID: 18948267, Sakaidani et al, 2011, PMID: 2215843). The gene was later cloned in mice and shown to rescue a posterior wing blistering phenotype resulting from RNAi knockdown of the Drosophila gene (Sakaidani et al, 2012, PMID: 22310717). O-GlcNAcylation of Notch1 enhances the binding of DLL1 and DLL4 to NOTCH1, thereby promoting downstream transcription of Notch target genes (Ogawa et al, 2015, PMID: 25488668). As the Notch signaling pathway is important in vascular development and angiogenesis, the role of EOGT is consistent with the features observed in patients with Adams-Oliver syndrome. Furthermore, the Eogt null mouse was shown to have vascular defects in the retina (Sawaguchi et al, 2017, PMID: 28395734). Of note, four of the six genes implicated in Adams-Oliver syndrome are in the Notch signaling pathway (RBPJ, NOTCH1, DLL4, EOGT (Tișa et al, 2025, PMID: 41516051). In summary, there is definitive evidence supporting the relationship between *EOGT* and Adams-Oliver syndrome 4, and autosomal recessive condition. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on July 6, 2026 (SOP Version 12).