Preimplantation exclusion of embryos at risk for prion diseases

Approximately 15% of human prion diseases are inherited disorders associated with PRNP gene mutations, such as familial Creutzfeldt–Jakob disease (fCJD). fCJD, a dominant late-onset neurodegenerative disorder with near 100% penetrance, is prevalent among Jews of Libyan descent having a common PRNP E200K founder mutation.¹ Mutation analysis can be used for diagnostic or predictive (presymptomatic) genetic testing in affected families. Offspring of affected individuals have a 50% chance of expressing the disorder; nevertheless, the age at onset varies between individuals.

Many patients at risk for fCJD prefer not to know their genetic status but still do not want to pass on the mutation, if it exists, to their children. Prenatal diagnosis through direct mutation analysis forces them to learn their own carrier status. A partial resolution for such problem was introduced by exclusion prenatal testing in which the fetus is tested for the presence of either allele of the relevant gene from the affected grandparent.² This procedure is designed to avoid the birth of at-risk offspring to an individual who chose not to perform a predictive test. A major …