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Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

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Abstract

A P102L point mutation in the prion protein gene (PRNP) usually causes Gerstmann–Sträussler–Scheinker disease (GSS), which is a rare hereditary transmissible spongiform encephalopathy (TSE). The clinical features include ataxia in 50s age group with subsequent dementia, spastic paraparesis and extrapyramidal signs. Many families have been reported from the Caucasian population, but only one from the Chinese. We hereby report a large Chinese family with P102L mutation of PRNP whose clinical manifestations at onset were intriguingly heterogeneous, either rapidly progressive dementia with scanty other neurological features or slowly progressive ataxia followed by cognitive impairment. The four-generation pedigree included eight patients with a mean age at onset of 36.9 ± 12.9 (mean ± SD) years. Mean disease duration to death in the four patients was 5.5 ± 1.7 (mean ± SD) years. Molecular analysis revealed a P102L mutation and M129 polymorphism in the PRNP gene in all affected individuals. TSE with P102L mutation of PRNP appears to have a remarkably variable phenotypic expressivity that may change with time and does not appear related to the codon 129 polymorphism.

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Acknowledgments

This research was funded by Taipei Veterans General Hospital, Taiwan (V96C1-025 and V97C1-069), and the National Science Council, ROC (NSC96-2314-B-010-036-MY3 and NSC97-2314-B-010-036-MY3).

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Authors and Affiliations

  1. Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan

    Nai-Fang Chi

  2. Department of Neurology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan

    Yi-Chung Lee & Bing-Wen Soong

  3. Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Chun Lu

  4. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

    Hsiu-Mei Wu

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  1. Nai-Fang Chi
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  2. Yi-Chung Lee
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Correspondence to Bing-Wen Soong.

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Chi, NF., Lee, YC., Lu, YC. et al. Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan. J Neurol 257, 191–197 (2010). https://doi.org/10.1007/s00415-009-5290-4

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