An Mutation in a Large Chinese Kindred With Familial Adenomatous Polyposis Was Identified Using Both Next Generation Sequencing and Simple STR Marker Haplotypes.

BACKGROUND

Familial 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 () 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 mutation, and demonstrated the practical use of -linked STR markers, which could be used to reduce misdiagnosis of prenatal diagnosis or preimplantation genetic diagnosis resulted from contamination or allele drop-out.

METHODS

Next-generation sequencing (NGS) was used to identify the possible 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 gene in the extended family.

RESULTS

We identified an : p.W553X mutation. The STR haplotype at the locus, A1B4C1, was shared by all clinically affected individuals with the : p.W553X mutation. In addition, the : p.D1822V variant was observed in 40% affected individuals and in two unaffected individuals.

CONCLUSION

We described a protein truncation mutation, : p.W553X; demonstrated the value of -linked STR markers (D5S299, D5S134, and D5S346) haplotypes; and suggested the potential role of these haplotypes in detecting loss of heterozygosity of the gene.