CASE REPORT
An autopsied case of Creutzfeldt-Jakob disease with mutation in the prion
protein gene codon 232 and type 1+2 prion protein
Yasushi Iwasaki1,*, Fuji Yokoi2, Shinsui Tatsumi1, Maya Mimuro1, Katsushige
Iwai3, Tetsuyuki Kitamoto4, Mari Yoshida1
Article first published online: 16 JAN 2013
DOI: 10.1111/neup.12013
© 2013 Japanese Society of Neuropathology
Keywords:
coarse-type PrP deposition; codon 232; Creutzfeldt-Jakob disease; prion
protein gene mutation; type 1+2 PrP
A 68-year-old Japanese man gradually showed abnormal behavior and gait
disturbance with bradykinesia. Slowly progressive dementia, including memory
disturbance and disorientation, was also observed. Cerebral cortical
hyperintensity on diffusion-weighted MRI was observed 6 months after onset. The
patient progressed to an akinetic mutism state with mild myoclonus, and atypical
periodic sharp-wave complexes were observed by electroencephalogram 13 months
after onset. He was clinically suspected of having atypical CJD and died after
19 months total disease duration. The brain weighed 1160 g and showed mild
atrophy of the cerebrum and cerebellum with ventricular dilatation. Spongiform
changes with varying vacuole size and gliosis was extensive in the cerebral
cortex and basal ganglia. Neuron loss in the cerebral cortex, basal ganglia and
thalamus was relatively mild. The cerebellum showed mild spongiform changes of
the molecular layer and mild neuron loss in the Purkinje cell layer. PrP
immunostaining showed mainly coarse-type combined with diffuse synaptic-type PrP
deposition in the cerebral gray matter. Some perivacuolar-type PrP deposition
was also present. Numerous plaque-type PrP depositions were observed in the
molecular layer of the cerebellum. Analysis of the PrP gene revealed a
methionine-to-arginine (Met-to-Arg) substitution at codon 232 (M232R) with Met
homozygosity at codon 129. Western blot analysis of protease-resistant PrP
indicated type 2 dominant PrP combined with type 1. Genetic CJD with M232R
substitution in the PrP gene has only been reported in Japan. Although two
clinical phenotypes (rapid-type and slow-type) were suggested in the M232R CJD
cases (despite the presence of the same PrP genotype), the pathological and
molecular backgrounds have not been well understood because there have only been
a few autopsied case reports. This is the first case report of M232R CJD
presenting with 1 + 2 PrP.
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settings (updated January 2013)
Friday, January 18, 2013
NPDPSC Gambetti et al pleading for more autopsies on suspect CJD cases Dear
Clinician:
TSS