Pregnancy after preimplantation genetic diagnosis exclusion testing for amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a disorder that involves progressive degeneration of motor neurons resulting in paralysis and death within 3-5 years. About 20% of ALS cases are due to a mutation in the copper/zinc superoxide dismutase (SOD-1) gene. A woman at 50% risk of a known familial SOD-1 mutation, who wanted to avoid passing on this mutation yet was not ready to confront her own genetic status, approached us to develop a preimplantation genetic diagnosis (PGD) exclusion test. PGD involves the biopsy of a day 3 embryo (at approximately the 8 cell stage of development) and requires diagnosis from a single cell. In exclusion testing, the gene inherited from the woman’s affected parent is identified using linked markers, and only embryos that do not inherit this gene are able to be transferred. A novel single cell multiplex diagnostic test was developed incorporating three informative markers flanking the SOD-1 gene. Eighteen embryos were tested for this woman and six were deemed suitable for transfer. One embryo was transferred to the woman’s uterus and a singleton pregnancy resulted. This is the first reported case of PGD exclusion testing for ALS.