Theoretically, other mechanisms such as exposure to a toxic chemical might lead to the conversion of PrP C to PrP Sc , but so far this has not been demonstrated. The identification of the human prion mutations listed in Table 2.2 were all made from 1989 onwards. Mutations occur in the familial forms of CJD, including GSS and FFI, and can sometimes be demonstrated in sporadic cases. They are detected by the analysis of the PRNP gene from DNA extracted from a small sample of blood or tissue. An affected individual passes the disease mutation on average to half his or her offspring, and therefore DNA analysis can be used to identify or exclude the disease in close relatives long before the onset of disease.
Point mutations result in the substitution of one amino acid for another.
For example, the prion protein gene specifies that proline is the amino acid at codon 102. A point mutation within the gene can change that amino acid from proline to leucine. Another common type of familial mutation results from the insertion of additional amino acids into the protein molecule. Specifically these are insertions of additional octapeptide repeats 3 in the prion protein. Other mutations result in polymorphic variation, ie, a change which is not associated with disease.