Open AccessPanencephalopathic C reutzfeldt‐ J akob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D 178 N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene
Author(s) -
Marcon Gabriella,
Indaco Antonio,
Di Fede Giuseppe,
Suardi Silvia,
Finato Nicoletta,
Moretti Valentino,
Micoli Sandro,
Fociani Paolo,
Zerbi Pietro,
Pincherle Alessandro,
Redaelli Veronica,
Tagliavini Fabrizio,
Giaccone Giorgio
Publication year - 2014
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12095
Subject(s) - prnp , neuropathology , cerebellum , biology , pathology , white matter , akinetic mutism , ataxia , mutation , cerebral cortex , atrophy , genetics , neuroscience , medicine , allele , gene , disease , magnetic resonance imaging , radiology
Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein ( PrP ) gene ( PRNP ). In subjects carrying the D 178 N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D 178 N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic C reutzfeldt‐ J akob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP Sc ( P archi classification). These findings underline the clear‐cut distinction between the neuropathological features of C reutzfeldt‐ J akob disease associated with D 178 N PRNP mutation and those of fatal familial insomnia.