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TPP2 mutation assoc...
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Reinthaler, Eva M.Med Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
TPP2 mutation associated with sterile brain inflammation mimicking MS
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
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2018
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-376411
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-376411URI
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https://doi.org/10.1212/NXG.0000000000000285DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Graf, ElisabethHelmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany
(författare)
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Zrzavy, TobiasMed Univ Vienna, Ctr Brain Res, Vienna, Austria
(författare)
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Wieland, ThomasHelmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany
(författare)
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Hotzy, Christoph
(författare)
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Kopecky, ChantalMed Univ Vienna, Dept Internal Med 3, Div Nephrol & Dialysis, Vienna, Austria
(författare)
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Pferschy, SandraMed Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
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Schmied, ChristianeMed Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
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Leutmezer, FritzMed Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
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Keilani, MohammadMed Univ Vienna, Rehabil & Occupat Med, Dept Phys Med, Vienna, Austria
(författare)
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Lill, Christina M.Univ Lubeck, Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Focus Program Translat Neurosci FTN, Dept Neurol, Mainz, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Neuroimaging Ctr NIC, Mainz, Germany
(författare)
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Hoffjan, SabineRuhr Univ Bochum, Dept Human Genet, Bochum, Germany
(författare)
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Epplen, Joerg T.Ruhr Univ Bochum, Dept Human Genet, Bochum, Germany;Univ Witten, Fac Hlth, ZBAF, Herdecke, Witten, Germany
(författare)
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Zettl, Uwe K.Univ Rostock, Neuroimmunol Sect, Dept Neurol, Rostock, Germany
(författare)
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Hecker, MichaelUniv Rostock, Neuroimmunol Sect, Dept Neurol, Rostock, Germany
(författare)
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Deutschlaender, AngelaJeweils Mayo Clin, Dept Neurol, Jacksonville, FL USA;Jeweils Mayo Clin, Dept Clin Genom, Jacksonville, FL USA;Jeweils Mayo Clin, Dept Neurosci, Jacksonville, FL USA
(författare)
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Meuth, Sven G.Univ Munster, Dept Neurol, Munster, Germany
(författare)
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Ahram, MamounUniv Jordan, Sch Med, Dept Physiol & Biochem, Amman, Jordan
(författare)
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Mustafa, BahaUniv Jordan, Sch Med, Dept Physiol & Biochem, Amman, Jordan
(författare)
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El-Khateeb, MohammedNatl Ctr Inst Diabet, Endocrinol & Genet NCDEG, Amman, Jordan
(författare)
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Vilarino-Guell, CartesUniv British Columbia, Dept Med Genet, Vancouver, BC, Canada
(författare)
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Sadovnick, DessaUniv British Columbia, Dept Med Genet, Vancouver, BC, Canada
(författare)
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Zimprich, FritzMed Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
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Tomkinson, Birgitta,1959-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Tomkinson(Swepub:uu)bto18995
(författare)
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Strom, TimHelmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany
(författare)
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Kristoferitsch, WolfgangSMZ Ost Donauspital, Karl Landsteiner Inst Neuroimmunol & Neurodegener, Vienna, Austria;SMZ Ost Donauspital, Inst Neuroimmunol & Neurodegenerat Disorders, Vienna, Austria
(författare)
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Lassmann, HansMed Univ Vienna, Ctr Brain Res, Vienna, Austria
(författare)
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Zimprich, AlexanderMed Univ Vienna, Dept Neurol, Vienna, Austria
(författare)
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Med Univ Vienna, Dept Neurol, Vienna, AustriaHelmholtz Zentrum Munchen, Inst Humangenet, Munich, Germany
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:NEUROLOGY-GENETICS4:62376-7839
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Reinthaler, Eva ...
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Graf, Elisabeth
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Zrzavy, Tobias
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Wieland, Thomas
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Hotzy, Christoph
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Kopecky, Chantal
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visa fler...
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Pferschy, Sandra
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Schmied, Christi ...
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Leutmezer, Fritz
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Keilani, Mohamma ...
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Lill, Christina ...
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Hoffjan, Sabine
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Epplen, Joerg T.
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Zettl, Uwe K.
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Hecker, Michael
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Deutschlaender, ...
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Meuth, Sven G.
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Ahram, Mamoun
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Mustafa, Baha
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El-Khateeb, Moha ...
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Vilarino-Guell, ...
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Sadovnick, Dessa
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Zimprich, Fritz
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Tomkinson, Birgi ...
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Strom, Tim
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Kristoferitsch, ...
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Lassmann, Hans
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Zimprich, Alexan ...
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