Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect
- 26 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in neurogenetics
- Vol. 21 (4), 251-257
- https://doi.org/10.1007/s10048-020-00618-1
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.This publication has 25 references indexed in Scilit:
- Genetic Creutzfeldt–Jakob disease with R208H mutation presenting as progressive supranuclear palsyMovement Disorders, 2012
- The first Chinese case of Creutzfeldt-Jakob disease patient with R208H mutation inPRNPPrion, 2011
- Prospective 10-year surveillance of human prion diseases in JapanBrain, 2010
- Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutationneurogenetics, 2008
- Y-Chromosome Based Evidence for Pre-Neolithic Origin of the Genetically Homogeneous but Diverse Sardinian Population: Inference for Association ScansPLOS ONE, 2008
- High incidence of genetic human transmissible spongiform encephalopathies in ItalyNeurology, 2005
- Creutzfeldt-Jakob disease associated with the R208H mutation in the prion protein geneNeurology, 2005
- Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob diseaseNeurology, 1996
- Genetic and population structure of four Sardinian villagesAnnals of Human Genetics, 1985
- Novel Proteinaceous Infectious Particles Cause ScrapieScience, 1982