Neuronal developmental disorders: Genetic variants in small non-coding RNAs discovered as a cause
Neuronal developmental disorders affect millions of people worldwide. Genetic causes are known for many of these disorders, but for around half of them they are still completely unclear. An international research team led by Prof. Dr. Christel Depienne from the Institute of Human Genetics at the Medical Faculty of the University of Duisburg-Essen and the University Medical Center Essen has now identified a large number of mutations in small nuclear RNAs (snRNAs) as a genetic cause. These snRNAs are an important component of the so-called "spliceosome", which is an important building block in the correct processing of genetic information.
"Our study is a milestone in research into genetic developmental disorders," emphasizes Prof. Dr. Christel Depienne, Professor of Molecular Genetics of Neurogenetic Developmental Disorders. "It provides the basis for improved diagnostic options and genetic counseling for future pregnancies and also provides new approaches for the development of therapeutic strategies."
The study, published in Nature Genetics, is based on the analysis of more than 23,000 patients with rare diseases*. It shows that mutations in the snRNA gene RNU4-2 are present in around 0.5% of cases and lead to ReNU syndrome, a rare neurodevelopmental disorder. A total of 145 new cases with (probably) disease-causing genetic variants in RNU4-2 were identified. A further 21 patients showed changes in the closely related snRNA genes RNU5B-1 and RNU5A-1, which are also associated with neuronal developmental disorders. Most of these gene mutations occurred spontaneously, i.e. they were not present in the parents, but were newly created in the affected children - especially on the maternal genome. "Depending on where exactly the mutation is located in the gene, the severity and severity of the symptoms differ significantly," explains Prof. Depienne.
Additional findings were provided by teams from the University Hospitals of Nantes (Dr. Benjamin Cogne) and Rouen (Dr. Camille Charbonnier), who identified biological markers in the blood, such as changes in RNA profiles and epigenetic signatures, which can provide further indications of the type of disease and could also enable more precise diagnosis of atypical courses in the future.
Another key contribution was made by the team led by Dr. Clément Charenton (IGBMC, Strasbourg), who, together with clinical partners, investigated the molecular mechanisms between gene mutation, cellular function and clinical phenotype.
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
Original publication
Caroline Nava, Benjamin Cogne, Amandine Santini, Elsa Leitão, François Lecoquierre, Yuyang Chen, Sarah L. Stenton, Thomas Besnard, Solveig Heide, Sarah Baer, Abhilasha Jakhar, Sonja Neuser, Boris Keren, Anne Faudet, Sylvie Forlani, Marie Faoucher, Kevin Uguen, Konrad Platzer, Alexandra Afenjar, et al.; "Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption"; Nature Genetics, 2025-5-16
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