Preimplantation genetic diagnosis (
PGD) has recently been performed for inherited
cancer predisposition determined by p53 tumour suppressor gene mutations, suggesting the usefulness of
PGD for
late onset disorders with
genetic predisposition, including those caused by the germline mutations of other tumour suppressor genes. Here
PGD was performed for two couples, one at risk for producing a child with maternally derived
neurofibromatosis type I (NF1), and the other with paternally derived
neurofibromatosis type II (NF2). The procedure involved a standard IVF protocol, combined with testing of oocytes or embryos prior to their transfer back to the patients. Maternal mutation Trp-->Ter (TGG-->TGA) in exon 29 of the NF1 gene was tested by sequential PCR analysis of the first and second polar bodies, and paternal L141P mutation in exon 4 of the NF2 gene by embryo biopsy at the cleavage stage. In both cases, multiplex nested PCR was applied, involving NF1 and NF2 mutation analysis simultaneously with the 3 and 2 linked markers, respectively. Of 57 oocytes tested in four
PGD cycles for NF1 mutation, 26 mutation-free oocytes were detected, from which eight were preselected for transfer, two in each cycle. These produced two clinical pregnancies, one confirmed to be mutation free by chorionic villus sampling but ending in a
stillbirth, and the other still ongoing. Of 18 embryos analysed in a cycle performed for NF2 mutation, eight mutation-free embryos were detected, three of which were transferred back to the patient, resulting in a singleton pregnancy and the birth of a mutation-free child. This suggests that
PGD is a useful approach for avoiding the birth of children with inherited
cancer predisposition, determined by NF1 and NF2 gene mutations.