Apparition of Germline Mutation c.1395-1397del of MUTYH in Algerian Consanguineous Family with Colorectal Cancer

Abstract

MUTYH is a glycosylase that removes adenine opposite 8-oxoguanine (OG) during base-excision repair of DNA. Variants of MUTYHdefective in functional activity lead to MUTYH-associated polyposis (MAP),autosomal recessive predisposition tocolorectal cancer (CRC).MAP combines clinical features with other hereditary CRC syndromesand exhibits phenotypic overlap, particularly with Lynch syndrome (LS). To determine the impact of MUTYH mutations in colorectal adenomas and cancer susceptibility, this prospective objective screens the MUTYHgene in seventeen Eastern Algerian families with clinically suspected LS but without mismatch repair (MMR) mutations. Methods: We examined the presence of the mutations in the probands and their relatives using direct sequencing of the entire coding region of the MUTYHgene. Results: The biallelic and monoallelic pathogenic MUTYHmutations, c.1395_1397del, were discovered in a consanguineous family with CRC and gastric cancer as a novel finding in our Eastern Algerian population. Conclusion: High rates of consanguinity in the Algerian population increase the risk of CRC caused by biallelic mutations in the MUTYHgene. In our families, the LS and MAP phenotypes might coexist. The inclusion of MUTYHtesting in the diagnostic strategy of LS-suspected patients should make carriers of mutations in this gene, as well as their first-line relatives, aware of their increased risk and encourage them to undergo early screening.