title: PGD for hereditary breast and ovarian cancer: the route to universal tests for BRCA1 and BRCA2 mutation carriers.
abstract: Preimplantation Genetic Diagnosis (PGD) is a method of testing in vitro embryos as an alternative to prenatal diagnosis with possible termination of pregnancy in case of an affected child. Recently, PGD for hereditary breast and ovarian cancer caused by BRCA1 and BRCA2 mutations has found its way in specialized labs. We describe the route to universal single-cell PGD tests for carriers of BRCA1/2 mutations. Originally, mutation-specific protocols with one or two markers were set up and changed when new couples were not informative. This route of changing protocols was finalized after 2 years with universal tests for both BRCA1 and BRCA2 mutation carriers based on haplotyping of, respectively, 6 (BRCA1) and 8 (BRCA2) microsatellite markers in a multiplex PCR. Using all protocols, 30 couples had a total of 47 PGD cycles performed. Eight cycles were cancelled upon IVF treatment due to hypostimulation. Of the remaining 39 cycles, a total of 261 embryos were biopsied and a genetic diagnosis was obtained in 244 (93%). In 34 of the 39 cycles (84.6%), an embryo transfer was possible and resulted in 8 pregnancies leading to a fetal heart beat per oocyte retrieval of 20.5% and a fetal heart beat per embryonic transfer of 23.5%. The preparation time and costs for set-up and validation of tests are minimized. The informativity of microsatellite markers used in the universal PGD-PCR tests is based on CEPH and deCODE pedigrees, making the tests applicable in 90% of couples coming from these populations.
authors.affiliation: Department of Clinical Genetics, University Medical Centre, Maastricht, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Drüsedau
authors.forename: Jos C
authors.initials: JC
authors.lastname: Dreesen
authors.forename: Inge
authors.initials: I
authors.lastname: Derks-Smeets
authors.forename: Edith
authors.initials: E
authors.lastname: Coonen
authors.forename: Ron
authors.initials: R
authors.lastname: van Golde
authors.forename: Jannie
authors.initials: J
authors.lastname: van Echten-Arends
authors.forename: Peter M M
authors.initials: PM
authors.lastname: Kastrop
authors.forename: Marinus J
authors.initials: MJ
authors.lastname: Blok
authors.forename: Encarna
authors.initials: E
authors.lastname: Gómez-García
authors.forename: Joep P
authors.initials: JP
authors.lastname: Geraedts
authors.forename: Hubert J
authors.initials: HJ
authors.lastname: Smeets
authors.forename: Christine E
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: Aimée D
authors.initials: AD
authors.lastname: Paulussen
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods; D011296:Prenatal Diagnosis / Q000379:methods
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human