Purpose: MUTYH-associated polyposis syndrome is inherited as a recessive trait and is characterized by the presence of colorectal adenomas and cancer predisposition. Carriers of biallelic mutations in the base excision repair gene MUTYH are exposed to an increased risk of colorectal cancer. The aim of this study was to investigate the pathogenicity of the 13-base-pair deletion, c.504 + 19_504 + 31del13, located on intron 6 of the MUTYH gene, which was identified in 2 unrelated Greek patients with MUTYH-associated polyposis.
Methods: Genomic DNA and total RNA were extracted from peripheral blood lymphocytes of 2 unrelated families with polyposis. Screening of the entire coding region of the APC gene and MUTYH gene was performed by direct sequencing.
Results: cDNA analysis of a patient homozygous for the c.504 + 19_504 + 31del13 mutation, and a patient heterozygous for the c.504 + 19_504 + 31del13/c.1437_1439delGGA mutations, revealed complete skipping of MUTYH exon 6. A part of the glycosylase catalytic domain, the pseudo-helix-hairpin-helix motif, is located within exon 6, which enhances the pathogenic effect of the mutation.
Conclusion: This study demonstrates a rare pathogenic MUTYH mutation that is possibly associated with a relatively severe MUTYH-associated polyposis phenotype, highlighted by early-onset colorectal cancer. These data can become useful in clinical practice for the appropriate surveillance and management of families with MUTYH-associated polyposis. It is evident that each MUTYH-associated polyposis case should be handled according to its distinct genotype, following a specific prophylaxis protocol to ensure cancer prevention.