Preimplantation genetic diagnosis of familial adenomatous polyposis

Familial adenomatous polyposis is a severe autosomal dominant cancer predisposition syndrome. It is characterized by the development of hundreds to thousands of polyps in the gastrointestinal tract, primarily in the colon, at a mean age of 16 years. Without a colectomy, colon cancer is inevitable. FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. A couple was referred to Monash IVF following a request to undertake preimplantation genetic diagnosis for FAP. The female proband had an AGTT deletion mutation in exon 15 of the APC gene. Analysis of the APC-linked marker D5S346 showed that the parental alleles were fully informative. A multiplex polymerase chain reaction (PCR) test was developed involving direct mutation detection and the co-analysis of D5S346 to identify allele drop out and avoid a misdiagnosis. The delAGTT mutation and D5S346 alleles were diagnosed by fluorescent PCR and allele sizing. Following standard hormone stimulation and IVF procedures, 14 oocytes were collected, 11 inseminated and nine embryos were biopsied on day 3. Of the nine embryos that were analysed, five embryos were affected and four were unaffected. Two unaffected embryos were transferred on day 4 resulting in a triplet pregnancy and the birth of three healthy babies.