Case Report: The Role of Molecular Analysis of the MUTYH Gene in Asymptomatic Individuals

Abstract

MUTYH-associated polyposis (MAP) is a rare hereditary condition caused by the biallelic mutation in the MUTYH gene encoding MUTYH glycosylase. This enzyme is a key member of the base excision repair (BER) pathway responsible for the repair of DNA lesions formed by reactive oxygen species (ROS). We report two cases of MAP. In case 1, a 67-year-old woman who presented with a personal history of colorectal and endometrial cancer and a family history of cancer syndromes underwent multigene panel testing that revealed a germline homozygous (biallelic) pathogenic variant c.1187G > A (p.Gly396Asp) in the MUTYH gene. Subsequent sequencing analysis performed in the offspring of the proband identified all three asymptomatic offspring as carriers of this pathogenic variant. In case 2, a 40-year-old woman with a strong family history of colorectal cancer [the proband’s sister was a carrier of the pathogenic variant c.536A > G (p.Tyr179Cys) of the MUTYH gene] and renal cancer underwent sequencing analysis of the MUTYH gene. The pathogenic heterozygous (monoallelic) variant c.536A > G (p.Tyr179Cys) of the MUTYH gene was identified in the proband. We found another pathogenic variant of the MUTYH gene—heterozygous (monoallelic) mutation c.1187G > A (p.Gly396Asp) in the genome of the proband’s husband. Molecular analysis of their offspring revealed that they are compound heterozygotes for MUTYH pathogenic variants c.536A > G (p.Tyr179Cys)/c.1187G > A (p.Gly396Asp). This paper shows the importance of genetic testing of asymptomatic relatives of the proband to ensure an early surveillance and management of individuals positive for pathogenic variant (s) in the MUTYH gene.

Design and fabrication of a microfluidic chip to detect tumor markers

“…1 Because bioactive tumor markers, including proteins, hormones, enzymes, polyamines and oncogene products, are secreted into the blood by tumor cells, they indirectly reect the status of the tumor and can therefore be used for diagnosis and treatment. 2,3 At present, commonly used detection methods for tumor markers include radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay and time-resolved uoroimmunoassay. 4 However, these tests need to be carried out in specialized biological laboratories within dedicated hospitals using instruments that need to be operated by quali-ed professional technicians.…”

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“…Biallelic pathogenic variants in the MUTYH gene cause MUTYH -associated polyposis (MAP). MAP is characterized by the presence of 15–100 colorectal polyps and an increased risk of colorectal adenomas and carcinomas [ 157 ]. Patients are diagnosed with MAP at a mean age of 45–50 years and median age of CCR onset is 48 [ 158 ].…”

“…Moreover, carriers of biallelic mutation have an increased risk of ovarian cancer, urinary bladder cancer, cancer of the upper gastrointestinal tracts, breast cancer, endometrial cancer, and skin cancer. Carriers of monoallelic mutation have an approximately 2.5-fold increased risk of CRC compared with the general population [ 159 ], but the risk of developing extraintestinal cancer in heterozygotes is still unclear [ 157 ].…”

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