A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family

Aušrinė Areškevičiūtė*, Peter Høgh, Anna Bartoletti-Stella, Linea Cecilie Melchior, Pia Rude Nielsen, Piero Parchi, Sabina Capellari, Helle Broholm, David Scheie, Eva Løbner Lund

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


Octapeptide repeat insertions (OPRI) found in the prion protein gene (PRNP) constitute a subgroup of pathogenic mutations linked to inherited prion diseases, a hallmark of which is a misfolded prion protein. The number of repeats in OPRI has been associated with different disease phenotypes. However, due to the rarity of the cases and heterogenous disease manifestations, the recognition and classification of these variants has been difficult. Here, we report the first Danish family, the fifth worldwide, carrying a novel 8-OPRI with a unique sequence of the additional 8 inserts: R1-R2-R2-R3-R2-R2-R2a-R2-R3g-R2-R2-R3-R4. The mutation was found on the allele coding for methionine at codon 129 in the PRNP gene. The clinical exome sequencing revealed that no other dementia-associated genes harbored pathogenic alterations. Mutation carriers had onset of symptoms in their early thirties, but disease duration varied from 5 to 11?years. Progressive dementia with psychiatric and motor symptoms were the most prominent clinical features. Clinical, pathological, and genetic characteristics of other 4 reported families with 8-OPRI were reviewed and compared with the findings in the Danish family.

Sider (fra-til)595-604
Antal sider10
TidsskriftJournal of Neuropathology and Experimental Neurology
Udgave nummer7
StatusUdgivet - 1 jul. 2019

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� 2019 American Association of Neuropathologists, Inc. All rights reserved.


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