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February 2020


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Loss of ADAMTS19 causes progressive non-syndromic heart valve disease. Nat Genet (2019), DZHK authors: Philipp Hofmann, Kirstin Hoff, Enrique Audain, Hans-Heiner Kramer, Marc-Phillip Hitz

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A genetic defect in the ADAMTS19 gene is one of the causes of leaking heart valves in humans. Researchers led by Professor Marc-Phillip Hitz, head of the Cardiogenetics working group at the Clinic for Congenital Heart Defects and Pediatric Cardiology at the Christian-Albrechts-University of Kiel (CAU) and endowed professor of the German Centre for Cardiovascular Research (DZHK), together with Professor Gregor Andelfinger from the Centre Hospitalier Universitaire Sainte-Justine Sainte in Montreal, Canada, published the results of their studies in the renowned journal "Nature Genetics" on 16 December.

Heart valves that leak or do not completely seal the heart chambers lead to an additional load on the heart. They occur in some people with age and some not. The question of whether there might be a predisposition for this was evident after two children in two blood-related families each have leaking heart valves. After examining the genetic material of the family members, the scientists were able to determine a loss of the ADAMTS19 gene in these children.

In the subsequent mouse experiment, mice with a switched off ADAMTS19 gene also had leaking heart valves. Both the tissue structure of the heart valves and their interaction with blood pressure were disturbed. A transcription factor involved in gene expression showed increased activity and led to a pathological alteration of the cellular structure of the heart valves.

The diagnosis "leaking heart valves" can be repaired - often without surgery - by inserting a new valve with the help of a catheter. However, this procedure does not lead to complete repair. The new findings might have an impact on further studies, which aim to influence the control loop disturbed by the genetic defect. It could stop the destruction of the heart valves of the affected patients, which progresses with age.

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