Tatjana Hirschmugl
Austrian Academy of Sciences
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Publication
Featured researches published by Tatjana Hirschmugl.
Journal of Clinical Immunology | 2016
Heidrun Boztug; Tatjana Hirschmugl; Wolfgang Holter; Karoly Lakatos; Leo Kager; Doris Trapin; Winfried F. Pickl; Elisabeth Förster-Waldl; Kaan Boztug
PurposeNF-κB signaling is critically important for regulation of both innate and adaptive immune responses. While activation of NF-κB has been implicated in malignancies such as leukemia and lymphoma, loss-of-function mutations affecting different NF-κB pathway components have been shown to cause primary immunodeficiency disorders. Recently, haploinsufficiency of NF-κB1 has been described in three families with common variable immunodeficiency (CVID).Methods and ResultsWe studied a patient with recurrent respiratory infections and bacterial parapharyngeal abscess. Immunological investigations revealed normal total B- cell numbers, but hypogammaglobulinemia, decreased frequencies of class-switched B cells and impaired T-cell proliferation. Targeted next-generation sequencing using a custom-designed panel comprising all known PID genes (IUIS 2014 classification) and novel candidate genes identified a novel heterozygous frameshift mutation in the NFKB1 gene leading to a premature stop codon (c.491delG; p.G165A*31). We could show that the mutation leads to reduced phosphorylation of p105 upon stimulation, resulting in decreased protein levels of p50. The further disease course was mainly characterized by two episodes of severe EBV-associated lymphoproliferative disease responsive to rituximab treatment. Due to disease severity, the patient is considered for allogeneic hematopoietic stem cell transplantation. Interestingly, the father carries the same heterozygous NFKB1 mutation and also shows decreased frequencies of memory B cells but has a much milder clinical phenotype, in line with a considerable phenotypic disease heterogeneity.ConclusionsDeficiency of NF-κB1 leads to immunodeficiency with a wider phenotypic spectrum of disease manifestation than previously appreciated, including EBV lymphoproliferative diseases as a hitherto unrecognized feature of the disease.
Haematologica | 2015
Baran Erman; Ivan Bilic; Tatjana Hirschmugl; Elisabeth Salzer; Deniz Ayvaz Çağdaş; Saliha Esenboga; Zuhal Akçören; Ozden Sanal; Ilhan Tezcan; Kaan Boztug
Combined immunodeficiencies (CIDs) comprise a heterogeneous group of monogenic disorders manifesting with lymphocyte defects, recurrent infections and dysregulated immune response. Recently, we and others have described clinical and molecular features of the combined immunodeficiency syndromes
Journal of Clinical Immunology | 2015
Ayca Kiykim; İsmail Öğülür; Safa Barış; Elisabeth Salzer; Elif Karakoc-Aydiner; Ahmet Ozen; Wojciech Garncarz; Tatjana Hirschmugl; Ana Krolo; Ayse Deniz Yucelten; Kaan Boztug; Isil B. Barlan
Protein kinase C delta (PRKCD) has essential functions in controlling B-cell proliferation and apoptosis, development of B-cell tolerance and NK-cell cytolitic activity. Human PRKCD deficiency was recently identified to be causative for an autoimmune lymphoproliferative syndrome like disorder with significant B-cell proliferation particularly of immature B cells. Here we report a child with a novel mutation in PRKCD gene who presented with CMV infection and an early onset SLE-like disorder which was successfully treated with hydroxychloroquine.
Traffic | 2014
Marco Sealey-Cardona; Katy Schmidt; Lars Demmel; Tatjana Hirschmugl; Tanja Gesell; Gang Dong; Graham Warren
The Sec16 homologue in Trypanosoma brucei has been identified and characterized. TbSec16 colocalizes with COPII components at the single endoplasmic reticulum exit site (ERES), which is next to the single Golgi stack in the insect (procyclic) form of this organism. Depletion of TbSec16 reduces the size of the ERES and the Golgi, and slows growth and transport of a secretory marker to the cell surface; conversely, overexpression of TbSec16 increases the size of the ERES and Golgi but has no effect on growth or secretion. Together these data suggest that TbSec16 regulates the size of the ERES and Golgi and this size is set for optimal growth of the organism.
Nucleic Acids Research | 2017
Heiko Müller; Raúl Jiménez-Heredia; Ana Krolo; Tatjana Hirschmugl; Jasmin Dmytrus; Kaan Boztug; Christoph Bock
Abstract Next generation sequencing is widely used to link genetic variants to diseases, and it has massively accelerated the diagnosis and characterization of rare genetic diseases. After initial bioinformatic data processing, the interactive analysis of genome, exome, and panel sequencing data typically starts from lists of genetic variants in VCF format. Medical geneticists filter and annotate these lists to identify variants that may be relevant for the disease under investigation, or to select variants that are reported in a clinical diagnostics setting. We developed VCF.Filter to facilitate the search for disease-linked variants, providing a standalone Java program with a user-friendly interface for interactive variant filtering and annotation. VCF.Filter allows the user to define a broad range of filtering criteria through a graphical interface. Common workflows such as trio analysis and cohort-based filtering are pre-configured, and more complex analyses can be performed using VCF.Filters support for custom annotations and filtering criteria. All filtering is documented in the results file, thus providing traceability of the interactive variant prioritization. VCF.Filter is an open source tool that is freely and openly available at http://vcffilter.rarediseases.at.
Blood | 2017
Laurène Pfajfer; Markus G. Seidel; Raïssa Houmadi; Javier Rey-Barroso; Tatjana Hirschmugl; Elisabeth Salzer; Inés M. Antón; Christian Urban; Wolfgang Schwinger; Kaan Boztug; Loïc Dupré
To the editor: The high motility of immune cells and their ability to establish cell-to-cell contacts depend on a tight regulation of actin cytoskeleton dynamics. Murine studies have identified the Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) as a key regulator of actin
Case Reports in Immunology | 2016
Neslihan Edeer Karaca; Guzide Aksu; Ezgi Ulusoy; Serap Aksoylar; Salih Gozmen; Ferah Genel; Sanem Eren Akarcan; Nesrin Gülez; Tatjana Hirschmugl; Kaan Boztug; Necil Kutukculer
Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.
British Journal of Haematology | 2018
Leo Kager; Raúl Jimenez Heredia; Tatjana Hirschmugl; Jasmin Dmytrus; Ana Krolo; Heiko Müller; Christoph Bock; Petra Zeitlhofer; Michael Dworzak; Georg Mann; Wolfgang Holter; Oskar A. Haas; Kaan Boztug
Establishing a precise diagnosis is essential in inborn haematological cytopenias to enable appropriate treatment decisions and avoid secondary organ damage. However, both diversity and phenotypic overlap of distinct disease entities may make the identification of underlying genetic aetiologies by classical Sanger sequencing challenging. Instead of exome sequencing, we established a systematic next generation sequencing‐based panel targeting 292 candidate genes and screened 38 consecutive patients for disease‐associated mutations. Efficient identification of the underlying genetic cause in 17 patients (44·7%), including 13 novel mutations, demonstrates that this approach is time‐ and cost‐efficient, enabling optimal management and genetic counselling.
Allergologia Et Immunopathologia | 2018
Samaneh Zoghi; Vahid Ziaee; Tatjana Hirschmugl; Raúl Jiménez-Heredia; Ana Krolo; Kaan Boztug; Nima Rezaei
INTRODUCTION AND OBJECTIVES Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE. PATIENTS AND METHODS Herein an eight-year-old girl with pSLE from consanguineous parents is reported. RESULTS Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges. CONCLUSIONS This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE.
Acta medica Iranica | 2016
Sima Shokri; Mohammad Nabavi; Tatjana Hirschmugl; Asghar Aghamohammadi; Saba Arshi; Mohamad Hassan Bemanian; Morteza Fallahpour; Rasool Molatefi; Mahsa Rekabi; Narges Eslami; Javad H. Ahmadian; Kian Darabi; Gholam Reza Sedighi; Maryam Monajemzadeh; Mohammadreza Modaresi; Nima Parvaneh; Kaan Boztug; Nima Rezaei