An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes
BackgroundFamilial 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...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00191/full |
| _version_ | 1828783354613334016 |
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| author | Qitao Zhan Liya Wang Xiangrong Xu Yan Sun Lejun Li Xuchen Qi Feng Chen Xiaoming Wei Michael L. Raff Ping Yu Fan Jin |
| author_facet | Qitao Zhan Liya Wang Xiangrong Xu Yan Sun Lejun Li Xuchen Qi Feng Chen Xiaoming Wei Michael L. Raff Ping Yu Fan Jin |
| author_sort | Qitao Zhan |
| collection | DOAJ |
| description | BackgroundFamilial 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.MethodsNext-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.ResultsWe 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.ConclusionWe 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. |
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| language | English |
| last_indexed | 2024-12-11T18:03:37Z |
| publishDate | 2020-03-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-f8b26adf572844778e98450e9caf58b32022-12-22T00:55:49ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-03-011110.3389/fgene.2020.00191483603An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker HaplotypesQitao Zhan0Liya Wang1Xiangrong Xu2Yan Sun3Lejun Li4Xuchen Qi5Feng Chen6Xiaoming Wei7Michael L. Raff8Ping Yu9Fan Jin10Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Neurosurgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaBGI-Shenzhen, Shenzhen, ChinaGenomics Institute, MultiCare Health System, Tacoma, WA, United StatesDepartment of Cell Biology and Medical Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaBackgroundFamilial 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.MethodsNext-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.ResultsWe 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.ConclusionWe 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.https://www.frontiersin.org/article/10.3389/fgene.2020.00191/fullfamilial adenomatous polyposisAPC geneSTR markernext generation sequencingmutation |
| spellingShingle | Qitao Zhan Liya Wang Xiangrong Xu Yan Sun Lejun Li Xuchen Qi Feng Chen Xiaoming Wei Michael L. Raff Ping Yu Fan Jin An APC Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes Frontiers in Genetics familial adenomatous polyposis APC gene STR marker next generation sequencing mutation |
| 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 | familial adenomatous polyposis APC gene STR marker next generation sequencing mutation |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00191/full |
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