Two Czech patients with familial adenomatous polyposis presenting mosaicism in APC gene

Urbanová, Markéta; Hirschfeldova, Katerina; Obeidová, Lena; Janošı́ková, Bohumila; Lastuvkova, Jana; Lukáš, Milan; Kotlas, Jaroslav; Stěkrová, J

doi:10.4149/neo_2018_180731n559

Cited by 3 publications

(1 citation statement)

References 29 publications

(45 reference statements)

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“…These studies identified deep intronic APC variants that result in pseudoexon formation [ 19 , 20 ]. Through the use of sensitive techniques, somatic APC mosaicism has been demonstrated in a minority of adenomatous polyposis patients [ 21 – 26 ]. In addition, using deep sequence analysis of APC in DNA isolated from multiple adenomas, mosaic variants were identified in 9 of 18 patients with 21 to 100 adenomas; in some of these cases, NGS also detected the variants in leukocyte DNA at low frequency [ 27 ].…”

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confidence: 99%

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

et al. 2021

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In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort.

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Section: Introductionmentioning

confidence: 99%

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

et al. 2021

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Paired Somatic-Germline Testing of 15 Polyposis and Colorectal Cancer–Predisposing Genes Highlights the Role of APC Mosaicism in de Novo Familial Adenomatous Polyposis

Rofes¹,

González²,

Navarro³

et al. 2021

The Journal of Molecular Diagnostics

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APC c.4621C>T variant causing Gardner's syndrome in a Han Chinese family may be inherited through maternal mosaicism

Cai

et al. 2021

Exp Ther Med

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Gardner's syndrome is a rare autosomal dominant hereditary disease that is characterized by multiple colorectal polyps combined with extra-colonic presentation (such as osteoma or desmoid tumors) of familial adenomatous polyposis syndrome. Gardner's syndrome is caused by the mutation of the adenomatous polyposis coli ( APC ) gene, which is located at 5q21. The aim of the current study was to investigate the APC gene mutations present in a Han Chinese family diagnosed with Gardner's syndrome. The 38-year-old proband presented with clinical symptoms, and was later diagnosed with Gardner's syndrome. Genomic DNA was extracted from the peripheral venous blood of 150 normal controls as well as the family members of the proband. Analysis of the respective APC gene sequences was performed using PCR amplification and Sanger sequencing. Pathogenesis associated with the APC mutation was investigated using reverse-transcription quantitative PCR and determined through bioinformatics approaches. Haplotype analysis was performed to identify the genetic source of the mutation(s). In the initial screening for APC variants, the APC c.4621C>T variant was detected in the proband and his son, but was not detected in the proband's affected mother. The mRNA expression changed significantly according to age and the presence of the mutation in the blood of the patients. Haplotype analysis suggested the presence of maternal mosaicism for this mutation. Haplotype analysis revealed that the APC c.4621C>T variant in a patient with Gardner's syndrome was most likely derived from his mother through mosaicism. These results indicate the necessity to verify the possibility of gonadal mosaicism when a proband diagnosed with Gardner's syndrome appears to exhibit a de novo mutation.

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Two Czech patients with familial adenomatous polyposis presenting mosaicism in APC gene

Cited by 3 publications

References 29 publications

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

Paired Somatic-Germline Testing of 15 Polyposis and Colorectal Cancer–Predisposing Genes Highlights the Role of APC Mosaicism in de Novo Familial Adenomatous Polyposis

APC c.4621C>T variant causing Gardner's syndrome in a Han Chinese family may be inherited through maternal mosaicism

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