Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis

Ann Clin Transl Neurol. 2018 Apr 26;5(6):777-783. doi: 10.1002/acn3.568. eCollection 2018 Jun.


Truncating mutations in PRNP have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel PRNP 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 PRNP truncating mutations and systemic abnormal PrP deposition and support a wider application of PRNP screening to include unsolved cases of familial autonomic neuropathy.

Grant support

This work was funded by Italian Ministry of Health grant RF2011‐02351092; Gino Galletti Foundation grant .