Ornithine transcarbamylase (OTC) deficiency is a severe X-linked metabolic disorder leading to hyperammonaemia and death shortly after birth. Prenatal diagnosis for OTC deficiency is available, but may require termination of pregnancy if affected. Thus there is a need for an option for pre-pregnancy testing, to pre-select OTC deficiency-free embryos for transfer, thus avoiding prenatal diagnosis and pregnancy termination. Preimplantation genetic diagnosis (PGD) for OTC deficiency has been developed, using sequential first and second polar body analysis; it was applied in a woman carrying the R26Q mutation in the exon 1 of OTC gene. The first and second polar bodies were removed following maturation and fertilization of oocytes in a standard IVF protocol, and analysed using a multiplex nested PCR. R26Q mutation was tested simultaneously with linked markers in six zygotes, resulting in detection of the embryos with a mutation-free maternal contribution; these were transferred back to the patient, yielding pregnancy and birth of a healthy child. This is the first PGD for OTC deficiency resulting in the birth of an unaffected child.
