PGD for cystic fibrosis patients and couples at risk of an additional genetic disorder combined with 24-chromosome aneuploidy testing

Preimplantation genetic diagnosis (PGD) for inherited disorders is presently applied for more than 300 different conditions. The most frequent PGD indication is cystic fibrosis (CF), the largest series of which is reviewed here, totalling 404 PGD cycles. This involved testing for 52 different CFTR mutations with almost half of the cases (195/404 cycles) performed for ΔF508 mutation, one-quarter (103/404 cycles) for six other frequent mutations and only a few for the remaining 45 CFTR mutations. There were 44 PGD cycles performed for 25 CF-affected homozygous or double-heterozygous CF patients (18 male and seven female partners), which involved testing simultaneously for three mutations, resulting in birth of 13 healthy CF-free children and no misdiagnosis. PGD was also performed for six couples at a combined risk of producing offspring with CF and another genetic disorder. Concomitant testing for CFTR and other mutations resulted in birth of six healthy children, free of both CF and another genetic disorder in all but one cycle. A total of 96 PGD cycles for CF were performed with simultaneous aneuploidy testing, including microarray-based 24-chromosome analysis, as a comprehensive PGD for two or more conditions in the same biopsy material.Preimplantation genetic diagnosis (PGD) for inherited disorders is now applied routinely for more than 300 different conditions. One of the first and currently most frequent PGD indications is cystic fibrosis (CF), for which 404 PGD cycles were performed in this centre. This involved testing for 52 different CF mutations, which has been extremely accurate in all but one case, due to an allele-specific amplification failure that was not sufficiently appreciated at the initial stage of PGD introduction. Almost three-quarters of these PGD cycles were for seven frequent mutations, including ΔF508, and only a few for the remaining 45 CFTR mutations. The experience of 44 PGD cycles for 25 affected homozygous or double-heterozygous CF patients, 18 male and seven female partners, is described, which involving the testing simultaneously for three mutations, with no misdiagnosis, resulting in birth of 13 healthy CF-free children. Also unique data on PGD for six couples at a combined risk of producing offspring with CF and another genetic disorder is presented, which resulted in birth of six healthy children, free from both CF and another genetic disorder. Because of the advanced reproductive age of some patients, 96 PGD cycles for CF were performed with simultaneous aneuploidy testing, including microarray-based 24-chromosome analysis, in an attempt to improve reproductive outcome.