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Genetic and molecular causes of heart defects

In rare cases, it sometimes happens that the organs are arranged incorrectly during embryonic development. Affected infants often suffer from severe heart defects and must be operated on immediately after birth. During a study conducted at the Competence Network for Congenital Heart Defects, a team of scientists supported by the Central Biobank Charité (ZeBanC) discovered that the mitochondria – the “powerhouses” of a cell – play an important role in arrangement of the organs.


Our heart forms in several phases, beginning from as early as the early embryonic period. In rare cases, it can happen that the organs are arranged incorrectly. About one in 15,000 newborns is affected. In a best-case scenario, the organs are simply mirror-inverted, without causing any major health issues. However, if the organs are entirely rearranged, so-called heterotaxy occurs and the affected newborns often have severe heart defects.

Dysfunction in the cell “powerhouses”?

During the embryonic phase, tiny “antennas” on the cells’ surface ensure that the heart and other organs end up in the “right place” – so arranged asymmetrically to each other in the body. According to the current state of research, these cell organelles known as cilia regulate the arrangement of the organs as early as the early embryonic phase. As part of a long-term study in collaboration with the Competence Network for Congenital Heart Defects, an international team of scientists led by Prof. Dr. Melanie Philipp and PD Dr. Martin Burkhalter found decisive evidence that the mitochondria in the somatic cells influence the cilia’s development. The cell “powerhouses”, which are only a few micrometres in length, thus seem to play a role in the incorrect arrangement of organs. Mitochondria are referred to as “powerhouses”, as they supply the cells with energy.

The scientists found that the blood cells of heterotaxy patients contained significantly fewer mitochondria than healthy sample donors. They also encountered certain gene mutations, which cause the mitochondria to dysfunction, more frequently in affected individuals. Some of the samples examined came from the national register for congenital heart defects of the Competence Network for Congenital Heart Defects. The Central Biobank Charité (ZeBanC) is responsible for processing and storing the national register samples as well as for DNA isolation.

Bridge between “antennas” and “powerhouse”

But how exactly do the activities of the cilia and mitochondria interact in the event of such a misarrangement? Using an electron microscope, the scientists were able to discover that a physical connection did indeed exist between the “antennas” and “powerhouses”. “Imagine it as a little bridge consisting of tubular protein structures known as microtubules,” says Melanie Philipp, explaining the connection scientists have discovered.

Dysfunctional “GPS”

The scientists at the same time came upon further significant evidence during the analysis of DNA samples from heterotaxy patients and animal models. They established that the cell “powerhouses” influence the length of the antenna-like cilia: the cilia on the cell surfaces were longer in the cases of reduced mitochondrial function. Their functionality was clearly limited compared to ‘healthy’ cilia. “This all suggests that when the mitochondria and cilia interact, a kind of GPS for the body develops for arrangement of the organs. The misarrangement of organs during embryonic development appears to involve genetically-induced misguided biochemical communication processes. These have a fatal impact on the development and arrangement of the organs even before the heart is formed,” said Martin Burkhalter, a biologist at the University of Tübingen, summarising the research team’s findings.

Decisive to future diagnostics and treatment

The scientists expect their findings to simplify the diagnosis of organ misarrangement and associated secondary diseases. In the long term, this should also help to improve the treatment options: “We had previously only been able to assign dysfunctional cilia to hereditary diseases. Now we know that the mitochondria also play a vital role. This means that we can shift the focus of our research and development work to the targeted production of functioning mitochondrial cells,” says Martin Burkhalter. This discovery could be decisive to the treatment of heterotaxy as well as other hereditary diseases.

Cooperation with the Central Biobank Charité

Scientists require suitable samples (e.g. blood and tissue) to achieve meaningful research results in the field of congenital heart defects and heart diseases diagnosed in childhood and adolescence. The Competence Network for Congenital Heart Defects works closely with the Central Biobank Charité (ZeBanC). Samples from more than 8,000 donors are collected, processed and stored here uniformly according to the highest scientific standards under ISO-certified conditions.


Source: The original text was published on the website of the Competence Network for Congenital Heart Defects.

Photo credits: Adobe Stock


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