Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Int J Clin Oncol. 2018 Jun;23(3):497-503. doi: 10.1007/s10147-017-1234-7. Epub 2018 Jan 12.
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.
碱基切除修复基因 MUTYH 是结直肠息肉综合征的致病基因，这是一种常染色体隐性疾病，与结直肠癌风险增加相关。由于很少有研究调查日本 MUTYH 变异患者的基因型-表型相关性，本研究旨在阐明通过筛查与遗传性结直肠息肉相关的致病基因检测到的日本 MUTYH 基因突变患者的临床病理特征。
在获得知情同意后，使用包括 MUTYH 在内的 26 个基因的靶向富集测序进行基因检测。
在 31 名疑似遗传性结直肠息肉的日本患者中，在 5 名患者中检测到 8 种 MUTYH 变异。在高加索人群中发现的 MUTYH 热点变异，即 p.G396D 和 p.Y179D，并不在检测到的变异中。在这 5 名患者中，有 2 名患者为双等位基因突变，诊断为 MUTYH 相关息肉病，而另外 2 名患者为单等位基因突变。1 名患者同一等位基因上存在 p.P18L 和 p.G25D 变异；然而，缺乏将这两个变异视为“致病性”的支持性数据。
在日本结直肠息肉病患者中发现了 2 名具有双等位基因突变的患者和另外 2 名具有单等位基因突变的患者。高加索人群 MUTYH 基因的热点变异不是日本患者的热点。
