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01-10-2020 | Creutzfeldt-Jakob Disease | Original Article

Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect

Authors: Marta Melis, Andrea Molari, Gianluca Floris, Sarah Vascellari, Luisa Balestrino, Anna Ladogana, Anna Poleggi, Piero Parchi, Giovanni Cossu, Maurizio Melis, Sandro Orrù, Giovanni Defazio

Published in: Neurogenetics | Issue 4/2020

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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Title: Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect
Authors: Marta Melis
Andrea Molari
Gianluca Floris
Sarah Vascellari
Luisa Balestrino
Anna Ladogana
Anna Poleggi
Piero Parchi
Giovanni Cossu
Maurizio Melis
Sandro Orrù
Giovanni Defazio
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Keyword: Creutzfeldt-Jakob Disease
Published in: Neurogenetics / Issue 4/2020
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-020-00618-1

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Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect

Abstract

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Springer Medicine

Abstract

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