Characteristics of MUTYH variants in Japanese colorectal polyposis patients
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The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype–phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis.
After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH.
Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants ‘pathogenic’ were lacking.
Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.
KeywordsMUTYH gene Multiple colorectal tumors Hereditary colorectal tumor
We thank the patients and their family members for participation in the study.
All authors contributed to this work. MT performed data collection and in silico analysis, and wrote the manuscript; TY performed genetic counseling and wrote the manuscript; HE, YT, MK, YO, and HI performed genetic analysis; KK performed genetic counseling; and SH made histological diagnosis.
This study was supported in part by a Grant-in-aid for the Support Project of the Strategic Research Center in Private Universities from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan awarded to the Saitama Medical University Research Center for Genomic Medicine (S1311002), a Grant supported by the Program for an Integrated Database of Clinical and Genomic Information from Japan Agency for Medical Research and Development (AMED) and the Office of Metropolitan Hospital Management, Tokyo Metropolitan Government for their financial support.
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Conflict of interest
The authors declare that they have no competing interests.