A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family
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A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family. / Areškevičiūtė, Aušrinė; Høgh, Peter; Bartoletti-Stella, Anna; Melchior, Linea Cecilie; Nielsen, Pia Rude; Parchi, Piero; Capellari, Sabina; Broholm, Helle; Scheie, David; Lund, Eva Løbner.
I: Journal of Neuropathology and Experimental Neurology, Bind 78, Nr. 7, 01.07.2019, s. 595-604.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family
AU - Areškevičiūtė, Aušrinė
AU - Høgh, Peter
AU - Bartoletti-Stella, Anna
AU - Melchior, Linea Cecilie
AU - Nielsen, Pia Rude
AU - Parchi, Piero
AU - Capellari, Sabina
AU - Broholm, Helle
AU - Scheie, David
AU - Lund, Eva Løbner
N1 - © 2019 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
U2 - 10.1093/jnen/nlz037
DO - 10.1093/jnen/nlz037
M3 - Journal article
C2 - 31107536
VL - 78
SP - 595
EP - 604
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 7
ER -
ID: 233723050