Novel variant of unknown significance in MUTYH in a patient with MUTYH-associated polyposis: a case to reclassify

被引：2

作者：

Kidambi T.D. ^{[1
]}

Goldberg D. ^{[2
]}

Nussbaum R. ^{[3
]}

Blanco A. ^{[2
]}

Umetsu S.E. ^{[4
]}

Terdiman J.P. ^{[1
]}

Lee J.K. ^{[5
]}

机构：

[1] Division of Gastroenterology, University of California, San Francisco, 505 Parnassus Ave Room S357, San Francisco, 94143, CA

[2] Hereditary GI Cancer Prevention Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA

[3] Invitae Corporation, San Francisco, CA

[4] Department of Pathology, University of California, San Francisco, San Francisco, CA

[5] Department of Gastroenterology, Kaiser Permanente Northern California, San Francisco, CA

来源：

Clinical Journal of Gastroenterology | 2018年 / 11卷 / 6期

关键词：

Hereditary cancer syndrome; Multiple colorectal adenomas; MUTYH; MYH-associated polyposis; Polyposis;

D O I：

10.1007/s12328-018-0870-4

中图分类号：

学科分类号：

摘要：

MUTYH-associated polyposis (MAP) is a hereditary cancer syndrome that is caused by biallelic pathogenic variants in the MUTYH gene and should be evaluated for in patients with an attenuated colonic polyposis phenotype. Monoallelic pathogenic variants in MUTYH are associated with a moderate increased risk of colorectal cancer but not with the polyposis phenotype. We present a case of a patient presenting with multiple colonic adenomatous polyps, whose germline testing revealed a heterozygous pathogenic variant in MUTYH in exon 13, c.1187G > A (p.Gly396Asp) as well as a heterozygous variant of unknown significance (VUS) in MUTYH in exon 14, c.1379T > C (p.Leu460Ser). We interpret the VUS as pathogenic in light of the patient’s phenotype; the fact that the VUS was in trans with a known pathogenic variant; and because all the in silico predictors suggested, it was likely to be deleterious. This case highlights the importance of a gastroenterologist recognizing the indication for genetic testing in a patient with greater than ten adenomas, the importance of a genetic counselor in interpretation of results, and is the first report of the specific variant in the literature with clinical information to suggest that it is likely pathogenic. © 2018, Japanese Society of Gastroenterology.

引用

页码：457 / 460

页数：3

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