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Updated: Jul 5, 2025
A Simple Composite Phenotype Scoring System for Evaluating Mouse Models of Cerebellar Ataxia
Published on: May 21, 2010
Gerstmann-Sträussler-Scheinker Disease Presenting as Late-Onset Slowly Progressive Spinocerebellar Ataxia, and
Christopher D Stephen1,2,3, Claudio Melo de Gusmao4,5, Sharan R Srinivasan6
1Ataxia Center, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Background:
Genetic prion diseases, including Gerstmann-Sträussler-Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late-onset cases are rare.
Objective:
To compare a novel GSS phenotype with six other cases and present pathological findings from a single case.
Methods:
Case series of seven GSS patients, one proceeding to autopsy.
Results:
Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS.
Conclusions:
We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late-onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.
