Tylosis esophageal cancer (TOC) is an autosomal-dominant (AD) syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. The gene-disease relationship of RHBDF2 and TOC was first reported by Blaydon et al. 2012(PMID: 22265016). Five unique missense variants in the RHBDF2 gene were reported to segregate with disease in 6 families, suggesting heterozygous gain of function is the mechanism of tumorigenesis for this gene. This gene-disease relationship is further supported by several mouse models and functional alteration studies. In summary, RHBDF2 is definitively associated with Tylosis esophageal cancer (TOC). This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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