Gene plays important role in embryonic development

Study at the University of Bonn identifies gene that can cause malformations if altered

An international study led by the medical Faculty of the University of Bonn has identified a gene that plays an important role in the development of the human embryo. If it is altered, malformations of various organ systems can result. The gene emerged very early in evolution. It also exists in zebrafish, for example, and performs a similar function there. The results have now been published in the Journal of Medical Genetics.

The researchers tracked down the gene when they studied two individuals with congenital malformations. “It was a man and his niece,” explains Dr. Gabriel Dworschak. “Both had malformed kidneys, urinary tract and esophagus, and the man also had a malformed right arm and heart.”

The physician at the University Children’s Hospital in Bonn conducts research on rare genetic diseases at the Institutes of Anatomy and Human Genetics. When the team looked at the genetic makeup of the family members, they came across an anomaly: A gene called SHROOM4 was altered in affected individuals compared to healthy individuals.

SHROOM4 was already familiar from another context: It was known to play a key role in brain function. Mutations can result in intellectual impairment, epileptic seizures and behavioral abnormalities. “Our findings indicated though, that it may play a broader role in embryonic organ development,” Dworschak explains.

The team from Bonn searched internationally for other cases in which abnormalities in the SHROOM4 gene had also been found – and succeeded: “Together with our cooperation partners, this led us to four more affected individuals from three families,” says Prof. Dr. Heiko Reutter, who has since moved from the University Hospital Bonn to the University of Erlangen-Nuremberg. “All of them had the SHROOM4 gene altered, but not always in the same way.” […]

Participating Core Facilities: The authors acknowledge the support from the Zebrafish Core Facility.

Participating institutions and funding:
In addition to the University of Bonn and the University Hospital Bonn, the study involved Children’s Mercy Hospital (USA), the Medical University of Silesia (Poland), the University of Zielona Góra (Poland), the University of Southern Denmark (Denmark), the University of Cologne, the University of Heidelberg, the University of Erlangen-Nuremberg, Medeor Hospital Lodz (Poland), and Goethe University Frankfurt. The work was supported by the German Research Foundation (DFG), the BONFOR program of the University Hospital Bonn, the Else Kröner-Fresenius Foundation, the Luise and Horst Köhler Foundation, and the National Institutes of Health (USA).

Publication: C. M. Kolvenbach et al.: X-linked variations in SHROOM4 are implicated in congenital anomalies of the urinary tract, the anorectal, the cardiovascular, and the central nervous system; Journal of Medical Genetics; DOI: 10.1136/jmg-2022-108738