Israeli Scientists Make Breakthrough with Williams Syndrome

Dr. Boaz Barak from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University

Researchers at Tel Aviv University say they have made a breakthrough and uncovered new factors linked to Williams Syndrome. Their findings may contribute to the development of treatments to enable the normal expression of genes essential for brain development in people suffering from the syndrome.

The research was led by Dr. Boaz Barak from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University and Dr. Asaf Marco from the Faculty of Agriculture, Food and Environment of the Hebrew University. The researchers examined human brain tissues taken from adults with and without Williams syndrome who died of causes unrelated to the syndrome and donated their brains to science.

The Cleveland Clinic explains that Williams syndrome is a rare genetic condition characterized by unique physical features, delays in cognitive development and potential cardiovascular problems. Children born with Williams syndrome can have a normal life expectancy but may develop side effects from the condition that can affect their prognosis.

The symptoms are diverse and include distinctive facial features (like broad forehead, full cheeks, upturned nose), cardiovascular issues (like aortic stenosis), mild-moderate intellectual disability, strong language skills, and a unique, outgoing personality. People with Williams syndrome are often described as endearingly friendly, empathetic, and musically inclined. They tend to excel in verbal communication and rote learning, but may face challenges with visual-spatial tasks.

“Williams syndrome is a rare, multisystem genetic syndrome that includes disorders in brain development that lead to heightened social interactions, mental retardation, and other characteristic features,” said Dr. Barak. “Past research has revealed that twenty-five genes are missing from the DNA on chromosome number seven of people with Williams syndrome, and the study of the syndrome to date has mainly focused on those missing genes and their functions.”

“We wanted to examine whether the syndrome is also characterized by defects in the genomes contained in brain cells which prevent the proper expression of essential genes. Specifically, we asked: ‘Is it possible that certain genes are not expressed properly in the brains of people with Williams syndrome due to the phenomenon of methylation – when a molecule known as a ‘methyl group’ is located on a certain gene that is present in the genome, preventing it from expressing itself properly?”.

To illustrate the phenomenon of the missing genes, Dr. Barak took an instruction book in which some of the pages were torn out. As a result of the missing pages, anyone following the instructions would make mistakes. Similarly, hiding some of the letters in the pages left in the book with a black marker would result in instructions being corrupted, just like methylation on an existing gene disrupts its expression.

Methylation is in many cases a normal mechanism in the cells of the body, as its role is to prevent expression of certain genes when appropriate. However, when there are disruptions in the correct application of methylation, the abnormal expression of the genes may lead to impairments in cell function, and subsequently cause damage to various organs, including to normal brain development.

The researchers found that indeed in people with Williams syndrome abnormal methylation does exist in this area of the brain, resulting in disruption of the normal expression of many genes related to the normal development of the brain’s neural functions, such as regulation of social behavior (people with Williams syndrome are known to be overly friendly), cognition, plasticity of the brain, and cell survival.

“Our research revealed new factors related to the disabilities that characterize Williams syndrome. Instead of focusing on the effects of the missing gene, as has been done until now, we shed light on many more genes that are expressed in a defective manner,” added Dr. Barak. “Building on our findings, it will be possible to focus future efforts on the development of targeted treatments that will reach the disrupted sites that we identified in the study in order to ‘correct’ the defective expressions.”