Does the clinical phenotype of fatal familial insomnia depend on PRNP codon 129 methionine-valine polymorphism?

Abstract

Fatal familial insomnia (FFI) is a rare, hereditary prion-protein disease. Methionine-valine polymorphism at codon 129 of the prion-protein gene (PRNP) determines the phenotype in other hereditary prion-protein diseases, but association with the clinical phenotype in FFI remains uncertain. Early clinical findings in FFI comprise disturbances of the sleep-wake cycle and mild neuropsychiatric changes which typically emerge during middle to late adulthood. Here we describe an unusually early onset and rapid progression of FFI associated with dorsal midbrain involvement in a female patient with PRNP mutation at codon 178 and homozygote methionine polymorphism at codon 129. Early dorsal midbrain involvement became apparent by total loss of REM sleep and isolated bilateral trochlear nerve palsy. Early onset and rapid progression disease type associated with dorsal midbrain involvement may indicate a different spatiotemporal distribution of the neurodegenerative process in FFI patients with PRNP mutation and codon 129 methionine homozygosity compared to methioninevaline heterozygosity.

DOI: 10.5664/jcsm.3286

Cite this paper

@article{Rupprecht2013DoesTC, title={Does the clinical phenotype of fatal familial insomnia depend on PRNP codon 129 methionine-valine polymorphism?}, author={Sven Rupprecht and Alexander Grimm and Torsten Schultze and Jan Zinke and Panagiota Karvouniari and Hubertus Axer and Otto W. Witte and Matthias Schwab}, journal={Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, year={2013}, volume={9 12}, pages={1343-5} }