Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype
A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominan...
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Wiley
2021-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2021/6610434 |
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| author | Li-jun Xie Dan-dan Ruan Jian-hui Zhang Yi Li Li Chen Mao-lin Yan Ming-dian Yu Jie-wei Luo Hui-zhen Zhang |
| author_facet | Li-jun Xie Dan-dan Ruan Jian-hui Zhang Yi Li Li Chen Mao-lin Yan Ming-dian Yu Jie-wei Luo Hui-zhen Zhang |
| author_sort | Li-jun Xie |
| collection | DOAJ |
| description | A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs∗31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp. |
| format | Article |
| id | doaj-art-302f7836a6154338993e6577f38f68b4 |
| institution | Kabale University |
| issn | 2291-2789 2291-2797 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-302f7836a6154338993e6577f38f68b42025-02-03T06:06:39ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972021-01-01202110.1155/2021/66104346610434Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp PhenotypeLi-jun Xie0Dan-dan Ruan1Jian-hui Zhang2Yi Li3Li Chen4Mao-lin Yan5Ming-dian Yu6Jie-wei Luo7Hui-zhen Zhang8Department of Oncology of Zhangzhou Traditional Chinese Medicine Hospital, Zhangzhou 363000, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaDepartment of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, ChinaA large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs∗31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp.http://dx.doi.org/10.1155/2021/6610434 |
| spellingShingle | Li-jun Xie Dan-dan Ruan Jian-hui Zhang Yi Li Li Chen Mao-lin Yan Ming-dian Yu Jie-wei Luo Hui-zhen Zhang Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype Canadian Journal of Gastroenterology and Hepatology |
| title | Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype |
| title_full | Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype |
| title_fullStr | Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype |
| title_full_unstemmed | Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype |
| title_short | Mutational Analysis of a Familial Adenomatous Polyposis Pedigree with Bile Duct Polyp Phenotype |
| title_sort | mutational analysis of a familial adenomatous polyposis pedigree with bile duct polyp phenotype |
| url | http://dx.doi.org/10.1155/2021/6610434 |
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