Apparition of germline mutation c.1395-1397del of MUTYH in Algerian consanguineous family with colorectal cancer

MUTYH is a glycosylase that removes adenine opposite 8-oxoguanine (OG) during base-excision repair of DNA. Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), autosomal recessive predisposition to colorectal cancer (CRC). MAP combines clinical features with other hereditary CRC syndromes, and 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 MUTYH gene 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 MUTYH gene. Results: The biallelic and monoallelic pathogenic MUTYH mutations, 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 Algerian population increase the risk of CRC caused by biallelic mutations in the MUTYH gene. In our families, the LS and MAP phenotypes might coexist.