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An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes
BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized primarily by the development of numerous adenomatous polyps in the colon and a high risk for colorectal cancer. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene. The proba...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064715/ https://www.ncbi.nlm.nih.gov/pubmed/32194643 http://dx.doi.org/10.3389/fgene.2020.00191 |
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author | Zhan, Qitao Wang, Liya Xu, Xiangrong Sun, Yan Li, Lejun Qi, Xuchen Chen, Feng Wei, Xiaoming Raff, Michael L. Yu, Ping Jin, Fan |
author_facet | Zhan, Qitao Wang, Liya Xu, Xiangrong Sun, Yan Li, Lejun Qi, Xuchen Chen, Feng Wei, Xiaoming Raff, Michael L. Yu, Ping Jin, Fan |
author_sort | Zhan, Qitao |
collection | PubMed |
description | BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized primarily by the development of numerous adenomatous polyps in the colon and a high risk for colorectal cancer. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene. The proband in this family was a 39-year-old female patient with the pathologic diagnosis of adenomatous polyps, and then a five-generation kindred with FAP was characterized in the following years. This article identified an APC mutation, and demonstrated the practical use of APC-linked STR markers, which could be used to reduce misdiagnosis of prenatal diagnosis or preimplantation genetic diagnosis resulted from contamination or allele drop-out. METHODS: Next-generation sequencing (NGS) was used to identify the possible APC mutations in an affected individual from a family with autosomal dominant colon cancer. Targeted sequencing then used to identify additional related individuals with the mutation. Three short tandem repeat (STR) loci, D5S299, D5S134, and D5S346, were used for PCR-based microsatellite analysis of the APC gene in the extended family. RESULTS: We identified an APC: p.W553X mutation. The STR haplotype at the APC locus, A1B4C1, was shared by all clinically affected individuals with the APC: p.W553X mutation. In addition, the APC: p.D1822V variant was observed in 40% affected individuals and in two unaffected individuals. CONCLUSION: We described a protein truncation mutation, APC: p.W553X; demonstrated the value of APC-linked STR markers (D5S299, D5S134, and D5S346) haplotypes; and suggested the potential role of these haplotypes in detecting loss of heterozygosity of the APC gene. |
format | Online Article Text |
id | pubmed-7064715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70647152020-03-19 An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes Zhan, Qitao Wang, Liya Xu, Xiangrong Sun, Yan Li, Lejun Qi, Xuchen Chen, Feng Wei, Xiaoming Raff, Michael L. Yu, Ping Jin, Fan Front Genet Genetics BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized primarily by the development of numerous adenomatous polyps in the colon and a high risk for colorectal cancer. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene. The proband in this family was a 39-year-old female patient with the pathologic diagnosis of adenomatous polyps, and then a five-generation kindred with FAP was characterized in the following years. This article identified an APC mutation, and demonstrated the practical use of APC-linked STR markers, which could be used to reduce misdiagnosis of prenatal diagnosis or preimplantation genetic diagnosis resulted from contamination or allele drop-out. METHODS: Next-generation sequencing (NGS) was used to identify the possible APC mutations in an affected individual from a family with autosomal dominant colon cancer. Targeted sequencing then used to identify additional related individuals with the mutation. Three short tandem repeat (STR) loci, D5S299, D5S134, and D5S346, were used for PCR-based microsatellite analysis of the APC gene in the extended family. RESULTS: We identified an APC: p.W553X mutation. The STR haplotype at the APC locus, A1B4C1, was shared by all clinically affected individuals with the APC: p.W553X mutation. In addition, the APC: p.D1822V variant was observed in 40% affected individuals and in two unaffected individuals. CONCLUSION: We described a protein truncation mutation, APC: p.W553X; demonstrated the value of APC-linked STR markers (D5S299, D5S134, and D5S346) haplotypes; and suggested the potential role of these haplotypes in detecting loss of heterozygosity of the APC gene. Frontiers Media S.A. 2020-03-04 /pmc/articles/PMC7064715/ /pubmed/32194643 http://dx.doi.org/10.3389/fgene.2020.00191 Text en Copyright © 2020 Zhan, Wang, Xu, Sun, Li, Qi, Chen, Wei, Raff, Yu and Jin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Zhan, Qitao Wang, Liya Xu, Xiangrong Sun, Yan Li, Lejun Qi, Xuchen Chen, Feng Wei, Xiaoming Raff, Michael L. Yu, Ping Jin, Fan An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title | An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title_full | An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title_fullStr | An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title_full_unstemmed | An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title_short | An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes |
title_sort | apc mutation in a large chinese kindred with familial adenomatous polyposis was identified using both next generation sequencing and simple str marker haplotypes |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064715/ https://www.ncbi.nlm.nih.gov/pubmed/32194643 http://dx.doi.org/10.3389/fgene.2020.00191 |
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