Open AccessThe Original Gerstmann‐Sträussler‐Scheinker Family of Austria: Divergent Clinicopathological Phenotypes but Constant PrP Genotype
Author(s) -
Hainfellner Johann A.,
BrantnerInthaler Sigrid,
Cervenáková Larisa,
Brown Paul,
Kitamoto Tetsuyuki,
Tateishi Jun,
Diringer Heino,
Liberski Pawel P.,
Regele Heinz,
Feucht Martha,
Mayr Norbert,
Wessely Peter,
Summer Kurt,
Seitelberger Franz,
Budka Herbert
Publication year - 1995
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.1995.tb00596.x
Subject(s) - prnp , neuropathology , pathology , biology , phenotype , amyloid (mycology) , dementia , amyloidosis , neurofibrillary tangle , genotype , alzheimer's disease , disease , genetics , medicine , gene , senile plaques
We present new data on the original Austrian kindred with Gerstmann‐Sträussler‐Scheinker disease (GSS) which encompasses currently 221 members in 9 generations. The mode of inheritance is autosomal dominant. Predominant clinical features are slowly progressive ataxia and late impairment of higher cerebral functins. In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopathological phenotype of Creutzfeldt‐Jakob disease (CJD). PRNP codon 129 was homozygous for methionine in both the historic and recent cases. Neuropathology confirms spongiosis of variable degree and numerous protease resistant / prion protein (PrP) amyloid plaques scattered throughout most of the brain as constant features in this family. Some amyloid deposits are surrounded by dystrophic neurites with accumulation of phosphorylated neurofilaments and abnormal organelles, reminiscent of Alzheimer‐type plaques. Severe telencephalic damage and a synaptic‐type fine granular immunoreactivity in laminar distribution in the cortex with anti‐PrP after hydrated autoclaving of sections were seen only in the recent patient. In conclusion, factors in addition to the PRNP genotype at codons 102 and 129 must play a role in determining clinicopathological characteristics of this inherited brain amyloidosis.