Importance

To describe the first case of preimplantation genetic diagnosis (PGD) and in vitro fertilization (IVF) performed for the prevention of genetic prion disease in the children of a 27-year-old asymptomatic woman with a family history of Gerstmann-Sträussler-Sheinker syndrome (GSS).

Observations

PGD and fertilization cycles resulted in detection of 6 F198S mutation-free embryos. Of these, 2 were selected for embryo transfer to the patient's uterus, yielding a clinical twin pregnancy and birth of healthy but slightly premature offspring with normal development at age 27 months.

Conclusion and relevance

IVF with PGD is a viable option for couples who wish to avoid passing the disease to their offspring. Neurologists should be aware of PGD to be able to better consult at-risk families on their reproductive choices.

Abstract A novel point mutation resulting in a glutamate-to-glycine substitution in PRNP at codon 200, E200G with codon 129 MV polymorphism (cis valine) and type 2 PrPSc was identified in a patient with a prolonged disease course leading to pathology-proven Jakob-Creutzfeldt disease. Despite the same codon as the most common genetic form of human PRNP mutation, E200K, this novel mutation (E200G) presented with a different clinical and pathological phenotype, including prolonged duration, large vacuoles, no vacuolation in the hippocampus, severe neuronal loss in the thalamus, mild cerebellar involvement, and abundant punctate linear and curvilinear deposition of PrPSc in synaptic boutons and axonal terminals along the dendrites.