Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene.
The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion protein (PrP) gene are described. Genetic analysis of the mutated allele revealed a sequence of five extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the  documented subjects. Neuopathological evaluation showed neuronal loss and gliosis in the neocortex of the 3 examined cases; spongiform degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology and distinct distribution was present in the cerebellem and neocortex ("blurred staining") of 2 examined cases. One subject showed features usually found in sporadic Creutzfeldt-Jacob disease with a punctate type of PrP deposition in the cerebellum. In addition, there were some plaque-like PrP aggregates morophologically similar to the other 2 cases in the molecular layer of the cerebellum, and unusual Prp immunoreactivity ("fleecy staining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.
Skworc
K H
KH
Institut für Neuropathologie, Germany.
Windl
O
O
Schulz-Schaeffer
W J
WJ
Giese
A
A
Bergk
J
J
Nägele
A
A
Vieregge
P
P
Zerr
I
I
Poser
S
S
Kretzschmar
H A
HA
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology; D004247:DNA; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010375:Pedigree; D011328:Prions / Q000235:genetics*; D020080:Tandem Repeat Sequences
D011328:Prions; D004247:DNA