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Fabišíková, Katarína and Hamidová, Olívia and Behulová, Regína Lohajová and Závodná, Katarína and Priščáková, Petra and Repiská, Vanda (2020) Case Report: The Role of Molecular Analysis of the MUTYH Gene in Asymptomatic Individuals. Frontiers in Genetics, 11. ISSN 1664-8021

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Abstract

Case Report: The Role of Molecular Analysis of the MUTYH Gene in Asymptomatic Individuals Katarína Fabišíková Olívia Hamidová Regína Lohajová Behulová Katarína Závodná Petra Priščáková Vanda Repiská

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.
12 15 2020 590486 10.3389/fgene.2020.590486 1 10.3389/crossmark-policy frontiersin.org true European Regional Development Fund http://dx.doi.org/10.13039/501100008530 313011V578 UK/208/2020 https://creativecommons.org/licenses/by/4.0/ 10.3389/fgene.2020.590486 https://www.frontiersin.org/articles/10.3389/fgene.2020.590486/full https://www.frontiersin.org/articles/10.3389/fgene.2020.590486/full Nat. Genet. Al-Tassan 30 227 2002 Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors 10.1038/ng828 Free Radic. Biol. Med. Banda 107 202 2017 Repair of 8-oxoG:a mismatches by the MUTYH glycosylase: mechanism, metals and medicine 10.1016/j.freeradbiomed.2017.01.008 Eur. J. Cancer Castillejo 50 2241 2014 Prevalence of germline MUTYH mutations among lynch-like syndrome patients 10.1016/j.ejca.2014.05.022 Gastroenterology Cleary 136 1251 2009 Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study 10.1053/j.gastro.2008.12.050 World J. Clin. Oncol. Curia 11 428 2020 MUTYH: Not just polyposis 10.5306/wjco.v11.i7.428 Hum. Mutat. Isidro 353 2004 Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas Clin. J. Gastroenterol. Kidambi 11 457 2018 Novel variant of unknown significance in MUTYH in a patient with MUTYH-associated polyposis: a case to reclassify 10.1007/s12328-018-0870-4 Clin. Genet. Landon 87 368 2015 Analysis of current testing practices for biallelic MUTYH mutations in MUTYH-associated polyposis 10.1111/cge.12375 J. Clin. Oncol. Lubbe 27 3975 2009 Clinical implications of the colorectal cancer risk associated with MUTYH mutation 10.1200/JCO.2008.21.6853 GeneReviews® [Internet] Nielsen 1993 2012 MUTYH polyposis [Updated 2019 Oct 10] Gastroenterology Nielsen 136 471 2009 Analysis of MUTYH genotypes and colorectal phenotypes in patients with MUTYH-associated polyposis 10.1053/j.gastro.2008.10.056 Crit. Rev. Oncol. Hematol. Nielsen 79 1 2011 MUTYH-associated polyposis (MAP) 10.1016/j.critrevonc.2010.05.011 J. Clin. Pathol. Nielsen 59 212 2006 Duodenal carcinoma in MUTYH-associated polyposis 10.1136/jcp.2005.031757 JAMA Oncol. Pearlman 3 464 2017 Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. 10.1001/jamaoncol.2016.5194 Cancer Rennert 118 1989 2012 MutYH mutation carriers have increased breast cancer risk 10.1002/cncr.26506 Best Pract. Res. Clin. Gastroenterol. Sampson 23 209 2009 MUTYH-associated polyposis 10.1016/j.bpg.2009.03.006 N. Engl. J. Med. Sieber 348 791 2003 Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH 10.1056/NEJMoa025283 Gastroenterology Terdiman 137 1883 2009 MYH-associated disease: attenuated adenomatous polyposis of the colon is only part of the story 10.1053/j.gastro.2009.10.017 Gastroenterology Vogt 137 1976 2009 Expanded extracolonic tumor spectrum in MUTYH-associated polyposis 10.1053/j.gastro.2009.08.052 Clin. Gastroenterol. Hepatol. Walton 14 986 2016 Frequency and features of duodenal adenomas in patients with MUTYH-associated polyposis 10.1016/j.cgh.2016.02.020 Gastroenterology Win 146 1208-11.e1 2014 Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer 10.1053/j.gastro.2014.01.022 Int. J. Cancer Win 139 1557 2016 Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH 10.1002/ijc.30197 Asian Pac. J. Cancer Prev. Zhu 12 1451 2011 AluYb8 insertion in the MUTYH gene and risk of early-onset breast and gastric cancers in the Chinese population

Item Type: Article
Subjects: GO for ARCHIVE > Medical Science
Depositing User: Unnamed user with email support@goforarchive.com
Date Deposited: 25 Jan 2023 10:23
Last Modified: 15 Feb 2024 04:18
URI: http://eprints.go4mailburst.com/id/eprint/132

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