Israeli Researchers Uncover Genetic Dysfunction Linked to Williams Syndrome

Jerusalem, 10 January, 2024 (TPS) -- Tel Aviv University researchers have unveiled a pivotal connection between the deletion of a specific gene associated with Williams syndrome and its related developmental disorders, potentially opening new avenues for targeted treatment.

Williams syndrome is a rare genetic disorder that affects various parts of the body. Individuals with Williams syndrome often experience developmental delays, particularly in motor skills and speech. Other health issues associated with Williams syndrome include cardiovascular problems like narrowed blood vessels and heart valve issues, as well as digestive problems. They might also have difficulties with coordination, and experience anxiety or phobias.

The disorder can be detected with testing during pregnancy. The range and severity of symptoms vary widely among individuals. Insights gleaned from the Israeli findings, which were recently published in the peer-reviewed Communications Biology, hint at the prospect of tailored treatment to enhance neural development and quality of life.

“Understanding the intricacies of mitochondrial function in neurological disorders like Williams syndrome is crucial for developing targeted interventions. These findings pave the way for potential treatments that improve mitochondrial function, not just in Williams syndrome but potentially in other conditions like Alzheimer’s, leveraging similar therapeutic strategies,” said Prof. Boaz Barak, who led the team.

“Mitochondria, responsible for generating cellular energy, play a crucial role in maintaining neural function. Any dysfunction in these cellular powerhouses can lead to a cascade of neurological disorders, spanning from neurodevelopmental conditions like Angelman syndrome and autism to neurodegenerative ailments such as Alzheimer’s and Parkinson’s,” he explained.

The focus of the study was on the Gtf2i gene, which encodes a transcription factor crucial for regulating numerous genes, including those involved in mitochondrial processes. Through meticulous genetic engineering techniques, the researchers observed that the absence of the Gtf2i gene led to an impaired formation of the mitochondrial network within nerve cells. As a result, the mitochondria struggled to function efficiently, leading to the accumulation of harmful substances within the cells.

Ariel Nir-Sade, for whom this groundbreaking research constitutes her doctoral thesis explained that the study involved culturing nerve cells from animal models of Williams syndrome and comparing them with and without the Gtf2i gene.

“We noted significant difficulties in mitochondrial development and function in cells lacking this gene. Subsequently, our examination of human brain tissue from individuals with Williams syndrome confirmed these findings, highlighting the crucial role of Gtf2i in mitochondrial regulation,” she said.