Germline mutations in patients with multiple colorectal polyps in China

Li, Chenguang; Jin, Peng; Yang, Lang; Zang, Wanchun; Kang, Qian; Li, Na; He, Yuqi; Xu, Junfeng; Zhang, Chen; Wang, Xin; Sheng, Jian-qiu

doi:10.1111/jgh.13776

Cited by 7 publications

(11 citation statements)

References 46 publications

(98 reference statements)

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“…In keeping with this, we observed that MUTYH c.934-2A > G variant alleles in heterozygous carriers (L130, L279, L522, and L239) were selectively expressed over wild-type alleles, suggesting that most of the MUTYH protein expressed may be defective. Notably, however, although heterozygous c.934-2A > G has been reported in several individuals with colorectal adenomas and carcinomas 11 – 14 , most variant carriers—estimated at an allele frequency of 1.4% in East Asians on the ExAC database, do not harbour an increased risk of developing cancers over the general population. This negates any clinically significant gene dosage or dominant-negative effect exerted by this variant, and suggests that additional “hits” must occur to confer additional risk.…”

Section: Discussionmentioning

confidence: 99%

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation

et al. 2020

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Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.

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Section: Discussionmentioning

confidence: 99%

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation

et al. 2020

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“…DNA libraries with an average insert size of 150 bp were sequenced on an Illumina NextSeq 500 or MiSeq platform (Illumina, San Diego, CA, USA). Genetic analysis was performed as previously described . The target gene panel comprised 19 genes related to hereditary CRC, including APC , MUTYH , MLH1 , MSH2 , MSH3 , MSH6 , PMS1 , PMS2 , BUB1 , BUB3 , EPCAM , PTEN , STK11 , SMAD4 , SETD2 , MAX , TSC2 , ATM , and FANCC .…”

Section: Methodsmentioning

confidence: 99%

“…Genetic analysis was performed as previously described. 13 The target gene panel comprised 19 genes related to hereditary CRC, including APC, MUTYH, MLH1, MSH2, MSH3, MSH6, PMS1, PMS2, BUB1, BUB3, EPCAM, PTEN, STK11, SMAD4, SETD2, MAX, TSC2, ATM, and FANCC. All variants found by next-generation sequencing (NGS) were confirmed with Sanger sequencing.…”

Section: Patientsmentioning

confidence: 99%

Clinical characterization and mutation spectrum in patients with familial adenomatous polyposis in China

Kang

Yang

et al. 2019

J of Gastro and Hepatol

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Background and Aim Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exist on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype–phenotype correlation in mutated patients. Methods Mutation screening of 46 unrelated probands was performed using multigene panels by next‐generation sequencing. Clinical data of the index were used to assess genotype–phenotype correlations. Results Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations, and 4 (8.70%) with both APC and MUTYH mutations. Ten APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH mutations was earlier than MUTYH mutation carriers and similar to APC mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers. Conclusion In this study, we show the importance of using multigene panels that allow for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analyses simultaneously.

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“…In another study with a larger sample, genetic testing detected a patient with a PMS1 gene biallelic germline pathogenic variant (c.488-489 insA). 51 Yang et al further explored adenomatous polyposis syndrome patients with unknown pathogenic variants. 52 The proband was a female.…”

Section: Mapmentioning

confidence: 99%

The Progress of Colorectal Polyposis Syndrome in Chinese Population

Yuan

Yang

Yuan

2023

Clin Colon Rectal Surg

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The pathogenesis, clinical phenotype, treatment strategy, and family management of hereditary tumor syndromes are different from those of sporadic tumors. Nearly a quarter of patients with colorectal cancer show significant familial aggregation and genetic predisposition, and 5 to 10% are associated with definite genetic factors. According to the clinical phenotype, it can be divided into nonpolyposis syndrome and polyposis syndrome. Among the polyposis syndrome patients with definite clinical symptoms, there are still some patients with unknown etiology (especially attenuated familial adenomatous polyposis), which is a difficult problem in clinical diagnosis and treatment. Therefore, for this rare disease, it is urgent to carry out multicenter studies, complete the gene variation spectrum, explore new pathogenic factors, and accumulate clinical experience. This article mainly introduces the research progress and related work of colorectal polyposis syndrome in China.

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Germline mutations in patients with multiple colorectal polyps in China

Abstract: A genetic screening strategy comprising 19 genes was effective to screen for hereditary CRC syndromes in patients with multiple colorectal polyps. The MUTYH germline mutation hotspots in Chinese patients may be different from those in Caucasian patients.

Cited by 7 publications

References 46 publications

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation

Clinical characterization and mutation spectrum in patients with familial adenomatous polyposis in China

The Progress of Colorectal Polyposis Syndrome in Chinese Population

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