Abstract
This Practice Point commentary describes the findings of a study by Webb et al. in which the researchers investigated phenotypic heterogeneity and disease-modifying factors in a large series of patients with inherited prion disease caused by a mutation in the PRNP gene that results in a Pro102Leu amino acid substitution. This mutation is traditionally associated with Gerstmann–Sträussler–Scheinker syndrome (GSS), and the clinical presentation in most patients in the study fitted into the GSS spectrum, but a subset presented with prominent cognitive impairment. In addition, the authors noted remarkable interfamilial and intrafamilial variability with respect to age at disease onset (range 27–66 years) and disease duration (range 7–132 months). Importantly, a polymorphism at PRNP codon 129 and the apolipoprotein E genotype were both identified as factors that modified the age at onset. These findings could have important implications for genetic counseling of individuals at risk from prion disease.
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References
Mead S (2006) Prion disease genetics. Eur J Hum Genet 14: 273–281
Hainfellner JA et al. (1995) The original Gerstmann–Sträussler–Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol 5: 201–211
Mead S et al. (2007) Inherited prion disease with 5-OPRI: phenotype modification by repeat length and codon 129. Neurology 69: 730–738
Reed LA et al. (2001) Phenotypic correlations in FTDP-17. Neurobiol Aging 22: 89–107
Rademakers R et al. (2007) Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C→T (Arg493X) mutation: an international initiative. Lancet Neurol 6: 857–868
Webb TE et al. (2008) Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain 131: 2632–2646
Palmer MS et al. (1991) Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352: 340–342
Dlouhy SR et al. (1992) Linkage of the Indiana kindred of Gerstmann–Sträussler–Scheinker disease to the prion protein gene. Nat Genet 1: 64–67
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Neumann, M. Phenotypic heterogeneity and genetic modifiers in prion disease caused by a Pro102Leu mutation in the PRNP gene. Nat Rev Neurol 5, 68–69 (2009). https://doi.org/10.1038/ncpneuro0998
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DOI: https://doi.org/10.1038/ncpneuro0998
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