Abstract
In genetic prion diseases (gPrD), five genetic variants (E200K, V210I, V180I, P102L, and D178N) are responsible for about 85% of cases. The R208H is one of the several additional rare mutations and to date, only 16 cases carrying this mutation have been reported worldwide. To describe the phenotypic features of 5 affected patients belonging to apparently unrelated Sardinian (Italian) families with R208H gPrD, and provide evidence for a possible founder effect are the aims of this study. The R208H PRNP mutation has a much higher relative frequency in Sardinia than elsewhere in Italy (72% vs. 4.4% of gCJD cases). Our cohort shared similar phenotypic features to the previously described patients with R208H-129M haplotype with most patients showing the classical Creutzfeldt-Jakob disease (CJD) phenotype. The analysis of 10 controls and 5 patients by NGS sequencing identified 4 haplotypes, 3 associated with the wild type variant, and one (H1) shared by all patients carrying the 208His variant. This is the first report of a regional cluster for R208H mutation in gPrD and the first report of the presence of a common ancestor for this Sardinian R208H cluster, confirming the probable consequences of genetic isolation process even for rare diseases.
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The authors confirm that the data supporting the findings of this study are available within the article. If needed, further data that support the findings of this study are available from the corresponding author, [MM], upon reasonable request.
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Melis, M., Molari, A., Floris, G. et al. Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect. Neurogenetics 21, 251–257 (2020). https://doi.org/10.1007/s10048-020-00618-1
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DOI: https://doi.org/10.1007/s10048-020-00618-1