Even before birth, an obstructed urethra can cause a variety of issues in the unborn child, ranging from mild urinary problems to kidney failure. This highly variable disease is called LUTO (lower urinary tract obstruction). Especially boys are affected. An international team of researchers led by the University of Bonn has now discovered a first gene involved in this rare disease. The results are now published in the “American Journal of Human Genetics”.
“In the worst case, the urinary retention caused by an obstruction of the urethra can result in damage to the kidneys and lungs prenatally,” says Dr. Alina Hilger of the Center for Pediatrics at the University Hospital Bonn (UKB).
Urinary retention leads to a lack of amniotic fluid, but this fluid is necessary for the lungs to develop properly in the amniotic sac. Hilger: “It is possible to save the fetus with surgery in the womb.” This complex and rare procedure is performed by Prof. Christoph Berg at the University Women's Hospital Bonn.
LUTO occurs comparatively rarely, only in about three out of 10,000 pregnancies. The few cases, however, show an occasional family accumulation and therefore seem to be hereditary. Until now, no gene causally associated with the disease and its heredity has been known.
An international team of researchers from Germany, the Netherlands, England, the USA and Poland, led by pediatricians, anatomists and human geneticists from the University Hospital Bonn, has now searched for the genetic origin of the disease.
Different variants of the BNC2 gene
The scientists compared the genetic material of four patients who had suffered from LUTO in varying degrees over three generations with that of healthy people. This revealed indications of mutations of the gene “BNC2”. The researchers then extended the study to 697 LUTO patients and uncovered three further variants of the BNC2 gene in these patients.
BNC2 encodes the protein “basonuclin 2”, which is believed to be involved in the processing of certain RNAs in the cell nucleus. “However, it is still unknown how the discovered mutations interfere with a biological mechanism that ultimately leads to the congenital narrowing of the urethra,” said lead author Caroline Kolvenbach from the UKB.
The researchers tested their findings on zebrafish. “This is a well-established animal model,” said Prof. Dr. Benjamin Odermatt from the Institute for Anatomy at the University Hospital Bonn. The fish reproduce and develop rapidly, which is why results are obtained fast. In addition, they are transparent during the larval stage and can therefore easily be screened for anatomical peculiarities.
First, the scientists knocked down the BNC2 gene in zebrafish. As a result, the zebrafish larvae developed a narrowing of their urinary tract. The researchers then transferred an intact human BNC2 copy into the manipulated fish embryos. This considerably decreased the number of urinary tract malformations in these fish.
However, the altered or mutated BNC2 copies found in the families were not able to rescue these malformations. “These experiments show that these variants or mutations found by us in BNC2 are actually responsible for LUTO,” says second lead author Dr. Gabriel Dworschak from the UKB.
New perspectives for genetic counseling
The team of scientists has thus discovered the first gene associated with LUTO. “At the same time, we have proven that LUTO has a genetic origin,” says Dr. Alina Hilger. “This also opens up new perspectives for genetic counseling of affected parents.”
Since many children with LUTO have impaired kidney function, the scientists assume that not only the urinary retention, but also the genetic defect itself impairs the function of the kidneys. By understanding the genetic causes, the scientists hope to eventually find an approach for a causal therapy for renal dysfunction in LUTO children.
Dr. Alina Hilger
Zentrum für Kinderheilkunde
Prof. Dr. Benjamin Odermatt
Rare Variants in BNC2 are Implicated in Autosomal Dominant Congenital Lower Urinary Tract Obstruction, The American Journal of Human Genetics, DOI: 10.1016/j.ajhg.2019.03.023
Johannes Seiler | idw - Informationsdienst Wissenschaft
Genetic differences between strains of Epstein-Barr virus can alter its activity
18.07.2019 | University of Sussex
Machine learning platform guides pancreatic cyst management in patients
18.07.2019 | American Association for the Advancement of Science
Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.
In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...
Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.
Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...
Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.
Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...
For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.
Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...
An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".
The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
19.07.2019 | Physics and Astronomy
19.07.2019 | Physics and Astronomy
19.07.2019 | Earth Sciences