Prion mutation D178N with highly variable disease onset and phenotype
- 1Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
- 2Department of Medical Genetics, University of Tübingen, Tübingen, Germany
- Professor L Schöls, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Hoppe-Seyler-Str. 3, University of Tübingen, 72076 Tübingen, Germany; ludger.schoels{at}uni-tuebingen.de
- Received 19 March 2008
- Revised 7 May 2008
- Accepted 13 May 2008
Abstract
Hereditary prion disease is a fatal genetic disorder of autosomal dominant inheritance. Recent phenotype–genotype correlation studies revealed a considerable clinical and pathological overlap for patients with the D178N mutation, suggesting a continous spectrum between fatal familial insomnia and Creutzfeldt–Jakob Disease phenotype. This report adds further evidence to this thesis from a large German prion pedigree with D178N mutation in the PRNP-gene. This pedigree shows an extensive variability in (1) age of disease onset, ranging from 19 to 72 years and including an asymptomatic 73-year-old gene carrier and (2) disease phenotype, including a Gerstmann–Straussler–Scheinker phenotype. These findings have substantial importance for genetic counselling of persons at risk.
Footnotes
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Competing interests: None.
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Patient consent: Obtained.
