uu.seUppsala universitets publikationer
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
TPP2 mutation associated with sterile brain inflammation mimicking MS
Med Univ Vienna, Dept Neurol, Vienna, Austria.
Helmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany.
Med Univ Vienna, Ctr Brain Res, Vienna, Austria.ORCID-id: 0000-0001-8909-1591
Helmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany.
Visa övriga samt affilieringar
2018 (Engelska)Ingår i: NEUROLOGY-GENETICS, ISSN 2376-7839, Vol. 4, nr 6, artikel-id UNSP e285Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
2018. Vol. 4, nr 6, artikel-id UNSP e285
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
URN: urn:nbn:se:uu:diva-376411DOI: 10.1212/NXG.0000000000000285ISI: 000455099800009PubMedID: 30533531OAI: oai:DiVA.org:uu-376411DiVA, id: diva2:1287385
Tillgänglig från: 2019-02-11 Skapad: 2019-02-11 Senast uppdaterad: 2019-02-11Bibliografiskt granskad

Open Access i DiVA

fulltext(674 kB)26 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 674 kBChecksumma SHA-512
ba9e1b428da3014ac9765b62cf6f760bdc1883abd084a4b46e93cee5abd25a295d262c24dacf2593b670e3cfd97ce9d984965c336e56e6fba1b3737b2a46863d
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Tomkinson, Birgitta

Sök vidare i DiVA

Av författaren/redaktören
Zrzavy, TobiasHecker, MichaelTomkinson, Birgitta
Av organisationen
Institutionen för medicinsk biokemi och mikrobiologi
Medicinsk genetik

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 26 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 63 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf