The present study was undertaken to elucidate germ line mutations of the base excision repair gene, MUTYH, in Japanese patients with adenomatous polyposis. We screened germ line mutations of adenomatous polyposis coli (APC) gene and MUTYH in 66 Japanese patients with adenomatous polyposis. APC was screened by the protein truncation test, while MUTYH was screened by polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing. The nicking assay was applied in order to evaluate the DNA glycosylase activity of the identified MUTYH variant. In this study, Seven MUTYH variants were identified in 16 of 21 APC-negative patients. Q324H mutation was the most frequent mutation, with an allele frequency of 49%. Two patients carried biallelic mutations other than Q324H; a patient had biallelic G272E and A359V mutations, while the other had compound heterozygotes of P18L and G25D mutations. Nicking assay for G272E using the corresponding mouse MUTYH mutant with G257E revealed that G272E is a variant to cause an impaired DNA glycosylase activity. Homozygous MUTYH mutation accounts for approximately 10% of Japanese patients with adenomatous polyposis. G272E may be one of the mutations specific to patients with adenomatous polyposis in East Asia.
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