A novel pathogenic splice acceptor site germline mutation in intron 14 of the APC gene in a Chinese family with familial adenomatous polyposis
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Dan Wang1,*, Shengyun Liang2,*, Zhao Zhang3,*, Guoru Zhao2, Yuan Hu4, Shengran Liang5, Xipeng Zhang3, Santasree Banerjee6,*
1Department of Pathology, Tianjin Medical University General Hospital, Tianjin 300052, China
2Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
3Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
4Department of Hematology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510006, China
5School of Life Science and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, China
6Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou 310000, China
*These authors contributed equally to this work
Santasree Banerjee, email: firstname.lastname@example.org
Xipeng Zhang, email: email@example.com
Keywords: familial adenomatous polyposis, APC gene, splice acceptor site mutation, targeted next-generation sequencing, colorectal cancer
Received: September 06, 2016 Accepted: January 27, 2017 Published: February 20, 2017
Familial adenomatous polyposis (FAP) is an autosomal dominant precancerous condition, clinically characterized by the presence of multiple colorectal adenomas or polyps. Patients with FAP has a high risk of developing colorectal cancer (CRC) from these colorectal adenomatous polyps by the mean age of diagnosis at 40 years. Germline mutations of the APC gene cause familial adenomatous polyposis (FAP). Colectomy has recommended for the FAP patients with significant polyposis. Here, we present a clinical molecular study of a four generation Chinese family with FAP. Clinical diagnosis of FAP has been done according to the phenotype, family history and medical records. Patient’s blood samples were collected and genomic DNA was extracted. In order to identify the pathogenic mutation underlying the disease phenotype targeted next-generation sequencing and confirmatory sanger sequencing has undertaken. Targeted next generation sequencing identified a novel heterozygous splice-acceptor site mutation [c.1744-1G>A] in intron 14 of APC gene, which is co-segregated with the FAP phenotypes in the proband and amongst all the affected family members. This mutation is not present in unaffected family members and in normal healthy controls of same ethnic origin. According to the LOVD database for Chinese colorectal cancer patients, in Chinese population, 60% of the previously reported APC gene mutations causes FAP, are missense mutations. This novel splice-acceptor site mutation causing FAP in this Chinese family expands the germline mutation spectrum of the APC gene in the Chinese population.
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