Familial Creutzfeldt-Jakob disease with an R208H-129V haplotype and Kuru plaques.
OBJECTIVE
To report the clinical and neuropathological features in the first patient seen, to our knowledge, with familial Creutzfeldt-Jakob disease and an R208H mutation associated with a Val/Val homozygosity at codon 129 in the prion protein gene (PRNP) and a type 2 protease-resistant prion protein.


RESULTS
A 61-year-old man with a long-standing history of memory loss and emotional disorders had an obvious behavioral change. Then he developed cerebellar ataxia, followed by cognitive decline. He had no myoclonus. Electroencephalography showed slow activity, and 14-3-3 protein detection was negative. Finally, the patient developed akinetic mutism and died 7 months after the onset of ataxia. Neuropathological examination showed severe spongiform changes in the frontal cortex and striatum and gliosis in the striatum and thalamus. Kuru plaques were noted in the cerebellum, notably in the molecular layer. Immunohistochemical findings showed granular, synaptic, perineuronal, and perivacuolar staining with antiprion antibodies. Kuru plaques were also stained.


CONCLUSIONS
This study strengthens the linkage of the R208H mutation to Creutzfeldt-Jakob disease and points to some particular features such as Kuru plaques and long-standing psychiatric signs.
Institut national de la santé et de la recherche médicale U466 and Department of Pathology, Rangueil Hospital, Toulouse, France. caline.basset@libertysurf.fr
Céline
C
Basset-Leobon
Emmanuelle
E
Uro-Coste
Katell
K
Peoc'h
Stéphane
S
Haik
Véronique
V
Sazdovitch
Mathieu
M
Rigal
Olivier
O
Andreoletti
Jean-Jacques
JJ
Hauw
Marie-Bernadette
MB
Delisle
D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000235:genetics*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006239:Haplotypes; D006639:Histidine / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D058225:Plaque, Amyloid / Q000473:pathology; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D014633:Valine / Q000235:genetics
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; D006639:Histidine; D001120:Arginine; D014633:Valine