A novel pathogenic single nucleotide germline deletion in APC gene in a four generation Chinese family with familial adenomatous polyposis

Sci Rep. 2017 Sep 27;7(1):12357. doi: 10.1038/s41598-017-10395-x.


Familial adenomatous polyposis (FAP) is an autosomal dominant precancerous condition which is associated with germline mutations of the APC gene. Clinically, FAP is characterized by the development of multiple colorectal adenomas or polyps which finally result in colorectal cancer by the 40 years age of the patient, if no surgical interventions have been undertaken. In this study, we present a clinical molecular study of a four generation Chinese family with FAP. Diagnosis of FAP was made on the basis of clinical manifestations, family history and medical (colonoscopy and histopathology) records. Genetic screening of the proband and all affected family members were performed by targeted next-generation sequencing and confirmatory Sanger sequencing. Targeted next generation sequencing identified a germline novel heterozygous single nucleotide deletion [c.3418delC; p.Pro1140Leufs*25] in exon18 of APC gene, which segregated with the FAP phenotypes in the proband and in all the affected family members whereas absent in unaffected family members as well as in normal healthy controls of same ethnic origin. Our present study expands the mutational spectrum of APC gene and provides evidence to understand the function of APC gene in FAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / diagnostic imaging
  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology
  • Adenomatous Polyposis Coli Protein / genetics*
  • Asian Continental Ancestry Group / genetics
  • Colon / diagnostic imaging
  • Colon / pathology
  • Colonoscopy
  • DNA Mutational Analysis
  • Female
  • Genetic Testing
  • Germ-Line Mutation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Rectum / diagnostic imaging
  • Rectum / pathology
  • Sequence Deletion


  • APC protein, human
  • Adenomatous Polyposis Coli Protein