A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease.

Complete sequencing of the prion protein open reading frame of a 68-year-old woman affected by a familial form of Creutzfeldt-Jakob disease (CJD) revealed a new mutation at codon 210 resulting in the substitution of isoleucine for valine. Moreover, a new 24-bp deletion encompassing codons 54 to 61 or 62 to 69 was found in the other allele. Four of the 17 asymptomatic relatives tested carry the 210 mutation. Two of them were 81 and 82 years old. Four of 22 patients with CJD whose recorded familial history was negative for demented illnesses, but none of 103 healthy control subjects, tested positive for the 210 mutation. These data suggest that the 210 mutation is associated with CJD, but that environmental factors or incomplete penetrance may contribute to the development of the disease. This finding also suggests that in Italy, familial CJD is more common than previously reported.