Genetics
What Does PRDM16 Do?
Zebrafish Help to Investigate Myocardial Insufficiency
When the Structure of the Myocardial Tissue is Impaired
In the majority of cases of congenital heart disease, the anatomy, that is, the heart’s structure, differs from that of heart-healthy people. In medicine, this is referred to as structural malformation. In addition to it, there are heart defects in which the structure of the muscle tissue of the heart chamber is impaired. This leads to cardiac insufficiency (cardiomyopathy). This disease is rather rare in childhood. With increasing age, however, its frequency increases.
Defect in the PRDM16 Gene
The causes of myocardial insufficiency (cardiomyopathy) vary and are not entirely known to this day. In many cases, an error in the genotype is responsible. Many different genes have already been identified as a cause of this myocardial insufficiency. Likewise, my colleagues and I were able to explore a gene which plays an important role in cardiomyopathy. In medical language, this gene is referred to as PRDM16. It influences the function of other genes that are important for the metabolism and the energy supply of individual cells.
How Does the Disease Develop?
Within our current study, we are trying to find out how frequently a genetic mutation occurs in the PRDM16 gene in patients with myocardial insufficiency. In addition, we seek to find the answer to the question of what exactly is happening when such a mutation leads to a disease. For this purpose, we are examining the genotype (DNA) of patients with myocardial insufficiency with respect to mutations in the known cardiomyopathy genes, as well as in the recently discovered PRDM16 gene.
How the Zebrafish Help us
Our quest for a better understanding of the disease mechanism is aided by an extraordinary animal: the zebrafish. Just like us humans, it is a mammal. Its heart, as well as its genotype, is structured in a similar manner as ours. Since zebrafish embryos develop outside of the mother’s body and are transparent during the first days of their development, heart development can be observed well in them. As soon as 24 hours after birth, we are able to see how their heart starts beating. After 48 hours, we are already able to start examining the heart function.
During this process, the genotype of the zebrafish will be changed in such a way as to feature the same gene mutation as in humans. After that, we will compare the heart function in this group of zebrafish with the heart function in healthy zebrafish. In addition, we intend to test a drug that has been developed during the project and which has meanwhile been patented. Its effect in zebrafish has the potential to give us some indication as to whether and how we might successfully use it in the treatment of patients with congenital cardiomyopathy.
-
Background
Discovery of PRDM16
Initial Research Results
© Nationales Register | privat
Dr. Anne-Karin Kahlert In 2013, a research team led by Sabine Klaasen and Anne-Karin Kahlert was able to discover and examine the PRDM16 gene, which is involved in cardiomyopathy. The new study called “The role of the co-transcription factor PRDM16 in cardiomyopathy" will interface with this research work. The researchers conducting the subsequent research are able to rely on the large data and sample basis provided by the National Register.
Learn more about the study design, material and methods, as well as the background of the study:
Publications
-
11.7.2013
Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.
Arndt AK, Schafer S, Drenckhahn JD, Sabeh MK, Plovie ER, Caliebe A, Klopocki E, Musso G, Werdich AA, Kalwa H, Heinig M, Padera RF, Wassilew K, Bluhm J, Harnack C, Martitz J, Barton PJ, Greutmann M, Berger F, Hubner N, Siebert R, Kramer HH, Cook SA, MacRae CA, Klaassen S
American journal of human genetics 93, 1, 67-77, (2013). Show this publication on PubMed.
-
In charge of the project:
-
© P. Benjamin
Dr. med. Anne-Karin Kahlert
Anne-Karin Kahlert leitet die Forschungsgruppe „Kandidatengene im Tiermodell“ am Institut für Klinische Genetik der Technischen Universität Dresden. More
Anne-Karin Kahlert studierte an der Universität Heidelberg und arbeitete anschließend als Assistenzärztin in der Klinik für angeborene Herzfehler und Kinderkardiologie in Kiel. Ihre Forschungstätigkeit führte sie an das Max-Delbrück-Centrum für Molekulare Medizin in Berlin sowie als Postdoktorantin an das Lehrkrankenhaus Brigham and Women's Hospital der Harvard Medical School in Boston, USA. Die mit dem DGPK Forschungsförderpreis 2018 ausgezeichnete Wissenschaftlerin arbeitet als Assistenzärztin in der Genetischen Ambulanz am Institut für klinische Genetik der TU Dresden und ist zudem als Wissenschaftliche Mitarbeiterin und Co-Arbeitsgruppenleiterin in der Klinik für angeborene Herzfehler und Kinderkardiologie in Kiel tätig.
© 
© 
©