WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor.
Gardner's syndrome is the association of familial adenomatous polyposis (FAP) with an anaphase promoting complex (APC) gene mutation and several extradigestive manifestations: osteomas, epidermal cysts and desmoid tumours.
Stemming from a mutation in the adenomatous polyposis coli (APC) gene, Gardner syndrome shares genetic correlations with the FAP phenotype; as a result, it becomes all the more crucial for physicians to be able to discern Gardner syndrome from other differential diagnoses such as Turcot syndrome, FAP, and other attenuated forms of familial polyposis.
Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome.
The E1573X mutation is the most distal mutation in the APC sequence reported to date as a mosaic and, interestingly, in the context of Gardner syndrome with extensive extracolonic features.
This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and familial adenomatous polyposis (FAP).
Somatic beta-catenin or APC gene mutations have been reported in < or =74% of sporadic deep fibromatoses and in virtually 100% of Gardner syndrome-associated fibromatoses, whereas genetic events in superficial fibromatoses remain less well characterized.
These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal carcinogenesis and that mutations at the APC gene can cause both adenomatous polyposis coli and Gardner's syndrome.
These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS.
These and published results including data on several constitutional deletions (M, SD, and brothers PW and ND) give a probable order of [cen] - [II227, proximal SD breakpoint] - [Cllpll] - [proximal PW/ND, M breakpoint(s), GM03314 breakpoint] - [ECB27] - [APC] - [YN5.48] - [distal PW/ND breakpoint] - [ECB134] - [distal M breakpoint] - [qter].
Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome.
Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin.
Somatic beta-catenin or APC gene mutations have been reported in < or =74% of sporadic deep fibromatoses and in virtually 100% of Gardner syndrome-associated fibromatoses, whereas genetic events in superficial fibromatoses remain less well characterized.