There has been sufficient evidence published associating the MSH6 gene with constitutional mismatch repair deficiency syndrome - a distinct disorder from Lynch syndrome - since the gene-disease relationship was first proposed by Menko, et al., (2004). Multiple case level studies have been performed with cMMRD patients that have variants in the MSH6 gene. Other mismatch repair (MMR) genes MLH1, MSH2 and PMS2 also causes constitutional mismatch repair deficiency syndrome. IHC and western blot revealed absence of MSH6 protein in patient cells. Multiple MSH6 deficient mouse and zebrafish models have been established to show consistent phenotypes with MMRCS patients by developing neurofibromas, non-Hodgkin’s lymphoma (NHL) and gastrointestinal (GI) tumors. All of these types of evidence are consistent with a definitive relationship between the MSH6 gene and constitutional mismatch repair deficiency syndrome.
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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