Novel PRNP sequence variant associated with familial encephalopathy.
Human transmissible spongiform encephalopathies (TSEs) are a group of chronic progressive neurodegenerative disorders that may be hereditary, infectious, or sporadic. Hereditary TSEs are associated with mutations in the PRNP gene on chromosome 20p12-pter. We report on a family in which seven patients developed limb and truncal ataxia, dysarthria, myoclonic jerks, and cognitive decline. The age of onset in the 30s, 40s, or 50s, prolonged disease duration, cerebellar atrophy on imaging, and the presence of synchronic periodic discharges on electroencephalogram suggested a familial encephalopathy resembling Gerstmann-Sträussler-Scheinker disease. A novel H187R mutation has been identified in affected, but not in unaffected, family members or unrelated controls suggesting a pathogenic role for this mutation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:653-656, 1999. Published 1999 Wiley-Liss, Inc.
Cervenáková
L
L
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland.
Buetefisch
C
C
Lee
H S
HS
Taller
I
I
Stone
G
G
Gibbs
C J
CJ
Brown
P
P
Hallett
M
M
Goldfarb
L G
LG
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics; D000682:Amyloid / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004739:England / Q000208:ethnology; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary; D014481:United States
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; D015252:Deoxyribonucleases, Type II Site-Specific; C037130:GCGC-specific type II deoxyribonucleases