Inherited prion encephalopathy associated with the novel PRNP H187R mutation: a clinical study.
OBJECTIVE
To describe a variant of prion encephalopathy associated with the recently identified H187R mutation in the prion protein (PRNP) gene.


METHODS
The authors studied a multigenerational American family with nine affected individuals. Clinical examination included imaging, EEG, and CSF analysis with 14-3-3 protein testing. Histopathology was characterized by examination of a brain biopsy from an H187R mutation-positive patient.


RESULTS
The disease in this family is caused by the PRNP H187R mutation and characterized by autosomal dominant inheritance, median age at disease onset of 42 years (range 33 to 50 years), and median duration of illness of 12 years (range 8 to 19 years). Clinical signs include progressive dementia, ataxia, myoclonus, and seizures. Histopathologic features consist of distinctive "curly" prion protein deposits with a strictly laminar distribution in the cerebral cortex and minimal astrogliosis in the absence of amyloid plaques or spongiosis.


CONCLUSIONS
A variant of prion encephalopathy associated with the novel H187R mutation in the PRNP gene displays distinctive clinical and immunostaining characteristics that further expand the boundaries of human prion disease.
Bütefisch
C M
CM
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Gambetti
P
P
Cervenakova
L
L
Park
K Y
KY
Hallett
M
M
Goldfarb
L G
LG
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics*; D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors