Fatal Familial Insomnia (FFI) is a genetic disorder caused by a mutation in the PRNP gene. The PRNP gene codes for the prion protein, thought to be involved in copper signaling and cell adhesion. For the mutation itself, at position 178, asparagine (N) replaces the wild type aspartic acid (D); D178N is the correct notation. However, what determines if someone shows the pathology of FFI or familial Cruetzfeldt-Jakob (fCJD), depends on another position on the mRNA that’s translated. The D178N mutation must be coupled with a methionine at position 129; this site is the valine/methionine polymorphism site.

Homozygotes at codon 129 show a shorter disease duration, more severe insomnia, and the disease is mostly restricted to the thalamus.

Heterozygous at codon 129 show a longer disease course and other symptoms, such as ataxia and dysarthria; the disease is not restricted to the thalamus, and can spread to other parts of the brain, such as the cerebral cortex.