Tyck till om SwePub Sök här!
onr:"swepub:oai:DiVA.org:uu-376411"
Sökning: onr:"swepub:oai:DiVA.org:uu-376411" > TPP2 mutation assoc...
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
TPP2 mutation associated with sterile brain inflammation mimicking MS
-
- Reinthaler, Eva M. (författare)
- Med Univ Vienna, Dept Neurol, Vienna, Austria
-
- Graf, Elisabeth (författare)
- Helmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany
-
- Zrzavy, Tobias (författare)
- Med Univ Vienna, Ctr Brain Res, Vienna, Austria
- visa fler...
- Hotzy, Christoph (författare)
- visa färre...
- (creator_code:org_t)
- 2018
- 2018
- Engelska.
- Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Reinthaler, Eva ...
- Graf, Elisabeth
- Zrzavy, Tobias
- Wieland, Thomas
- Hotzy, Christoph
- Kopecky, Chantal
- visa fler...
- Pferschy, Sandra
- Schmied, Christi ...
- Leutmezer, Fritz
- Keilani, Mohamma ...
- Lill, Christina ...
- Hoffjan, Sabine
- Epplen, Joerg T.
- Zettl, Uwe K.
- Hecker, Michael
- Deutschlaender, ...
- Meuth, Sven G.
- Ahram, Mamoun
- Mustafa, Baha
- El-Khateeb, Moha ...
- Vilarino-Guell, ...
- Sadovnick, Dessa
- Zimprich, Fritz
- Tomkinson, Birgi ...
- Strom, Tim
- Kristoferitsch, ...
- Lassmann, Hans
- Zimprich, Alexan ...
- visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Medicinska och f ...
- och Medicinsk geneti ...
- Artiklar i publikationen
- NEUROLOGY-GENETI ...
- Av lärosätet
- Uppsala universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
