title: A novel pathogenic large germline deletion in adenomatous polyposis coli gene in a Chinese family with familial adenomatous polyposis.
abstract: Germline mutations of the APC gene are associated with an autosomal dominant precancerous condition, termed familial adenomatous polyposis (FAP). FAP is clinically manifested by the presence of multiple colorectal adenomas or polyps. Gradually, these colorectal adenomas or polyps inevitably result in colorectal cancer by the third-to fourth decade of life. Surgical interventions or total proctocolectomy is the best possible treatment for FAP. Here, we present a clinical molecular study of a five generation Chinese family with FAP. Diagnosis of FAP was made on the basis of clinical manifestations, family history and medical (colonoscopy and histopathology) records. Blood samples were collected and genomic DNA was extracted. Genetic screening of the APC gene was performed by targeted next-generation sequencing and quantitative real-time PCR. Targeted next generation sequencing identified a novel heterozygous large deletion [exon5-exon16; c.423_8532del] of APC gene, which segregated with the FAP phenotypes in the proband and in all the affected family members. Unaffected family members and normal controls did not carry this deletion. In the Chinese population, most of the previously reported APC gene mutations are missense mutations. This is the first report describing the largest deletion of the APC gene in the Chinese population associated with FAP.
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Shengran
authors.initials: S
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pathology, Tianjin Medical University General Hospital, Tianjin 300000, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China.
authors.forename: Xipeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Huishuang
authors.initials: H
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Rong
authors.affiliation: Xiamen Prenatal Diagnosis Center, Xiamen Maternal and Child Health Care Hospital, Xiamen 361000, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Santasree
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002681:China; D003113:Colonoscopy; D005091:Exons; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein
keywords: APC gene; colorectal cancer; familial adenomatous polyposis; large exon deletion; targeted next-generation sequencing