Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp rather than to the age of onset of polyps.ENG was first reported in relation to autosomal dominant JPS in 2005 (Sweet et al., PMID: 16287957). ENG (Endoglin) is a component of the transforming growth factor beta (TGFB) receptor complex and binds TGFB1 with a crucial role in vascular development and angiogenesis. Haploinsufficient variants account for over 85% of patients with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) and have been found to have a Definitive relationship with HHT (see separate curation). Variants in ENG genes were subsequently reported in patients with JPS without overlapped HHT phenotype. Therefore, per the ClinGen Lumping and Splitting Working Group this curation solely focuses on JPS phenotype with regard to curating the limited information available for this split curation. Seven missense variants that have been reported in eight probands in three publications (PMIDs: 16287957, 17204053, 23399955) are included in this curation. All of these JPS associated ENG variants are variants of uncertain pathogenicity (0.3 point). There were two research articles showing endoglin expression was increased in various cancer tissues including colon (1 point). Combination of genetic and experimental evidence has not demonstrated convincing definitive validity of ENG gene in inherited JPS. In summary, there is limited evidence to support this gene-disease relationship.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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