Gene Dyrk1a Linked to Coronary heart Defects in Down Syndrome Recognized

Gene Dyrk1a Linked to Heart Defects in Down Syndrome Identified

Leveraging genetic mapping, scientists pinpointed a gene on human chromosome 21 named Dyrk1a. Within the mouse mannequin of Down syndrome, having three copies of this gene results in coronary heart defects. Whereas Dyrk1a has been related to cognitive impairment and facial modifications in Down syndrome, its involvement in coronary heart growth was beforehand unknown. (1 Trusted Supply
Elevated dosage of DYRK1A results in congenital coronary heart defects in a mouse mannequin of Down syndrome

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Down syndrome impacts round 1 in 800 new births and is attributable to an additional third copy of chromosome 21. About half of infants born with Down syndrome have coronary heart defects, akin to a failure of the center to separate into 4 chambers, leaving a ‘gap within the coronary heart’.

If the center defects are very critical, high-risk surgical procedure may be wanted quickly after delivery and other people typically require ongoing monitoring of the center for the remainder of their life. Subsequently, higher remedy choices are wanted and this should be guided by information of which of the additional 230 genes on chromosome 21 are chargeable for the center defects. However earlier than this examine the identification of those causative genes was not recognized.

In analysis printed at present in Science Translational Medication, the workforce on the Crick and UCL studied human Down syndrome fetal hearts in addition to embryonic hearts from a mouse mannequin of Down syndrome.

An additional copy of Dyrk1a turned down the exercise of genes required for cell division within the creating coronary heart and the operate of the mitochondria, which produce power for the cells. These modifications correlated with a failure to accurately separate the chambers of the center.

Unveiling the Lacking Hyperlink in Down Syndrome Coronary heart Defects

The workforce discovered that whereas Dyrk1a is required in three copies to trigger coronary heart defects in mice, it was not adequate alone. Thus, one other unknown gene should even be concerned within the origin of coronary heart defects in Down syndrome. The workforce is at present looking for this second gene.

Dyrk1a codes for an enzyme referred to as DYRK1A. The researchers examined a DYRK1A inhibitor on mice pregnant with pups that mannequin the hearts defects in Down syndrome, as their hearts had been forming. When DYRK1A was inhibited, the genetic modifications had been partially reversed and the center defects within the pups had been much less extreme.

Victor Tybulewicz, Group Chief of the Immune Cell Biology Laboratory & Down Syndrome Laboratory, mentioned: “Our analysis reveals that inhibiting DYRK1A can partially reverse modifications in mouse hearts, suggesting that this can be a helpful therapeutic method.


“Nonetheless, in people the center varieties within the first 8 weeks of being pregnant, probably earlier than a child might be screened for Down syndrome, so this is able to be too early for remedy. The hope is {that a} DYRK1A inhibitor may affect the center later in being pregnant, and even higher after delivery. These are potentialities we’re at present investigating.”

This analysis varieties a part of the lab’s total objective to know the genetics behind all points of Down syndrome.


Eva Lana-Elola, Principal Laboratory Analysis Scientist on the Crick, and co-first creator, mentioned: “It was outstanding that simply restoring the copy variety of one gene from 3 to 2 reversed the center defects within the mouse mannequin for Down syndrome. We’re now aiming to know which of the opposite genes on this further chromosome are concerned. Although Dyrk1a isn’t the one gene concerned, it’s clearly a significant participant in many various points of Down syndrome.”

Rifdat Aoidi, Postdoctoral Mission Analysis Scientist on the Crick, and co-first creator, mentioned: “We don’t but know why the modifications in cell division and mitochondria imply the center can’t accurately kind chambers. Dysfunction within the mitochondria has additionally been linked to cognitive impairment in Down syndrome, so boosting mitochondrial operate might be one other promising avenue for remedy.”


  1. Elevated dosage of DYRK1A results in congenital coronary heart defects in a mouse mannequin of Down syndrome – (



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