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Research Topics



Genetics of pulmonary arterial hypertension


In cooperation with Prof. Dr. med. Grünig at Thoraxklinik, Heidelberg University Hospital, we are searching for genetic causes of pulmonary arterial hypertension (PAH).


In the majority of patients with familial PAH, heterozygous mutations are identified in the BMPR2 (Bone Morphogenetic Protein Receptor 2) gene. In patients with sporadic, idiopatic PAH (not familial), BMPR2 mutations can be detected only in part of the cases. Apart from mutations in the BMPR2 gene, there are other genes which can be responsible for this disease, too. Among them, the following genes have been identified: ALK1 (Activin A receptor type II-like 1) and ENG (Endoglin). In families with PAH combined with Osler-Weber-Rendu disease and in patients with infantile PAH, mutations in the ALK1 gene and in the ENG gene were found. In a few cases, mutations in these two genes were detected in patients with idiopatic/hereditary PAH. Penetrance of the mutations is very variable, the factors which influence penetrance being largely unidentified. In our research cooperation, we are aiming at identifying further genes which cause PAH as well as genetic factors which modify the penetrance.


Cooperation partners:

Prof. Dr. med Ekkehard Grünig, Zentrum für Lungenhochdruck Pulmonale Hypertonie, Thoraxklinik, Heidelberg
Dr. sc. hum Christine Fischer, AG Genetische Epidemiologie/Biostatistik, Institut für Humangenetik


Staff members:

Christina Alessandra Eichstaedt, PhD

Jie Song, MD

Evelyn Fey

Nina Litters

Chromosomal imbalances in AL amyloidosis


In cooperation with the coordinating investigator of the GERAMY project, PD Dr. med. Schönland, we are participating in the BMBF subproject 2 in the genetic analysis of monoclonal plasma cells in order to improve understanding of amyloidogenesis and prognosis of light chain amyloidosis.


Immunoglobulin light chain (AL) amyloidosis is a malign bone marrow plasma cell disorder. The malign plasma cells produce dysplastic proteins, the light chains, and release them into the blood. Gradually, more and more of these protein molecules (so-called amyloid) are deposited in different organs, inflicting lasting damage on them.

In the past few years, genomic alterations have increasingly been found to be essential pathogenetic and prognostic factors which strongly influence therapy of other plasma cell diseases, e.g. the multiple myeloma (MM). Regarding AL amyloidosis, the alterations have not been addressed so far. There are indications of the translocation t(11;14) acting as negative prognostic factor.

In order to improve understanding of formation of amyloid fibrils as well as the prognosis of light chain amyloidosis, chromosomal aberrations are being analysed with micoarray comparative genomic hybridization (Array-CGH) and interphase fluorescence in situ hybridization (iFish). Our aim is to identify those genomic alterations which show a strong correlation to the response to chemotherapy and to the prognosis of AL amyloidosis.


Nationaler Forschungsverbund

GERAMY - Deutsches Konsortium für die systemische Leichtketten-Amyloidose – BMBF (Projektleitung: PD Dr. med. Stefan Schönland, Innere Medizin V, Universitätsklinik Heidelberg)–

Subproject 2: Genetic analysis of monoclonal plasma cells in order to improve understanding of formation of amyloid fibrils as well as prognosis for AL amyloidosis.

Project management GERAMY:

PD Dr. med. Stefan Schönland, Innere Medizin V, Amyloidose-Zentrum, Universitätsklinikum Heidelberg


Project management – subproject 2:

 Prof. Dr. sc. hum. Anna Jauch, Institut für Humangenetik

Co-submitters – subproject 2:

Dr. rer. nat. Katrin Hinderhofer, Institut für Humangenetik
Dr. phil. nat. Rolf Köhler, Institut für Humangenetik


Staff members (array analyses):

Evelyn Fey

Nina Litters



Genetics of Fabry disease in infancy


Headed by PD Dr. Dr. Ries (Zentrum für Kinder- und Jugendmedizin, Universitäts­klinik Heidelberg), the frequency of a rare heriditary metabolic disorder, Fabry disease, is being investigated by a multi centre screening trial. Affected patients often suffer from recurring abdominal or limb pains. As the illness progresses, heart and kidneys might be affected and strokes might occur. Thus, early detection is crucial. This disease can be treated with an enzyme replacement therapy. In this cooperation, we are acting as reference laboratory for female trial patients which show rheumatological symptoms or abdominal pain. For these patients, we are carrying out molecular genetic examinations of the GLA gene - located on the X chromosome - which is responsible for the disorder. For male patients, direct biochemical analyses are possible and are being conducted at the metabolic centre (Stoffwechselzentrum im Zentrum für Kinder- und Jugendmedizin, Universitätsklinik Heidelberg).


Principal applicant:

PD Markus Ries, MD PhD MHSc FCP, Morbus Fabry Studie, Zentrum für Kinder- und Jugendmedizin, Universitätsklinik Heidelberg


Staff members:

Anke Gerhardt

Nina Litters

Repeat expansion at the FMR1 locus: Premature ovarian insufficiency


In cooperation with Prof. Dr. rer. nat. Vogt (Sektion Molekulare Genetik und Fertilitätstörungen, Frauenklinik, Universitätsklinik Heidelberg), we are looking for the genetic causes of infertility in women. In this context, at our institute we are conducting Southern Blot and PCR analyses at the FMR1 locus.


Cooperation partner:

Prof. Dr. rer. nat. Peter H. Vogt

Dr. med. Julia Rehnitz

Birgitta Messmer

Sektion Molekulare Genetik und Fertilitätstörungen, Frauenklinik, Universitätsklinik Heidelberg

Staff members:

Dr. rer. nat. Ulrike Barth

Birgit Hanel


Repeat expansion at the FMR1 locus: Fragile X syndrome


Trinucleotid repeat expansions in the genome can cause neurological diseases, e.g. the fragile X syndrome. So far, the underlying mechanisms causing these expansions at the FMR1 locus remain unidentified to a very large extent. Therefore, in situ examinations of the cell nucleus’ chromatin are necessary in order to better understand the supra molecular mechanisms in individual cells. By means of a „super-resolution localization microscopy” (Spectral Position Determination Microscopy; SPDM) combined with “nano-probing” using COMBO-FISH (COMBinatorial Oligonucleotide FISH), insight into the genome’s nanoarchitekture can be gained. These investigations are carried out at the Kirchoff-Institut, and their results concerning the repeat length are compared with the results from the Southern Blot analyses from the laboratory of molecular genetic diagnostics.


Exzellenzinitiative II / Zukunftskonzept / Innovationsfonds FRONTIER:

Optical Sequencing of Fragile X-Syndrome Associated Repeat Expansion DNA Units in Intact Cell Nuclei by means of COM-BO-FISH and Localization Nanoscopy  PDF



Prof. Dr. rer. nat. Michael Hausmann, Kirchhoff-Institut, Universität Heidelberg
Dr. rer. nat. Katrin Hinderhofer, Institut für Humangenetik

Staff members:

Evelyn Fey

Birgit Hanel