Abstract

We report the clinical progression of the Gerstmann-Sträussler-Scheinker disease (GSS) in a family of Alsatian origin. The age of onset and duration of evolution were variable. The clinical picture became more complex over the generations: isolated dementia in the first generations, then, more recently, a triad of pyramidal, pseudobulbar syndrome and dementia associated with symptoms indicating spread of damage to the spinal cord and cerebellum. Study of the prion gene showed that in all patients analyzed and in 10 healthy family members, there is a double mutation of codon 117 leading to loss of the restriction site PvuII and to the replacement of an alanine by a valine. We did not find the mutation of codon 102 reported in 5 GSS families. The role of these mutations in the pathogenesis of the disease is unclear: marker for a particular susceptibility to the encephalopathies due to the prion, or direct role in the disease? Further study of the family, particularly the healthy carriers, could suggest the answer. GSS seems to be an especially useful model for the study of the role of a foreign abnormal protein in the synthesis and regulation of host proteins.