Genetic causes of developmental disorders: New discoveries revealed!

Genetic causes of developmental disorders: New discoveries revealed!

Neurodevelopmental disorders are a serious health problem that affects millions of people worldwide. An international research team led by Prof. Dr. Christel Depienne from the Institute for Human Genetics at the University of Duisburg-Essen has now identified genetic causes that can lead to the development of these disorders. In their comprehensive study, which in Nature Genetics was published, the researchers analyzed over 23,000 patients with rare diseases and discovered mutations in small nuclear RNAs (snRNAs) as possible triggers.

The genetic causes of around 50 percent of neurodevelopmental disorders are still unclear. While the study identified a significant number of mutations in the snRNA gene RNU4-2 that lead to ReNU syndrome, the researchers were also able to discover variants in related genes such as RNU5B-1 and RNU5A-1. A total of 145 new cases with potentially disease-causing variants were documented, with most gene changes occurring spontaneously, often in the maternal genome. The severity of symptoms varied depending on the location of the mutation.

New discoveries in developmental disorders

In parallel to these findings, researchers at Leipzig University Medical Center reported two specific genetic mutations that can trigger neurodevelopmental disorders in children. These discoveries, published in scientific journals, show that more than 50 percent of cases of intellectual disability or epilepsy remain unexplained. In one of the cases examined, a mutation was found in a child suffering from early-onset epilepsyCHKA genenoted. This change affects the enzyme cascade that produces membrane building blocks.

Another case involved a younger patient with developmental disorders who had mutations in theATP2B1 genehave been identified that encodes a calcium pump, which is crucial for neurological functions.

Collaboration and further development in research

The identification of these genetic variations is supported by international collaborations and large databases such as ClinVar, in which new genetic variants are documented. It is still only possible to make a diagnosis in 40-50 percent of cases. The further development of sequencing technologies, such as Next Generation Sequencing (NGS), plays a central role.

Additionally, in a separate study,ESAM genediscovered that has not previously been associated with rare diseases. This research was carried out on 13 people, including four fetuses, and included participants from different countries such as Italy, the USA and France. Those affected often show symptoms such as global developmental delay, intellectual disability and epileptic seizures.

The ESAM gene encodes a cell-cell junction protein that plays an important role in the blood-brain barrier. The discovery of the bi-allelic variants of the ESAM gene suggests that there may be new classifications for diseases with endothelial dysfunction called tight junctionopathies.

These advanced genetic studies enable a better understanding of the molecular mechanisms behind neurodevelopmental disorders, which is of great importance for both research and clinical practice. Such findings are crucial for developing treatment options and making early diagnoses.