Two novel <i><scp>PRNP</scp></i> truncating mutations broaden the spectrum of prion amyloidosis

Abstract

Truncating mutations in <i>PRNP</i> have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel <i>PRNP</i> stop-codon mutations (p.Y163X, p.Y169X) in two Italian kindreds. Disease typically presented in the third or fourth decade with progressive autonomic failure and diarrhea. Moreover, one proband (p.Y163X) developed late cognitive decline, whereas some of his relatives presented with isolated cognitive and psychiatric symptoms. Our results strengthen the link between <i>PRNP</i> truncating mutations and systemic abnormal PrP deposition and support a wider application of <i>PRNP</i> screening to include unsolved cases of familial autonomic neuropathy.