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Scientists find clues to mystery of Williams Syndrome’s peculiar symptoms

October 11, 2018

Patients with Williams Syndrome often are extremely social and possess a remarkable affinity and talent for music. They also experience life-threatening cardiovascular problems and developmental disabilities. The mystery is what happens during development to cause such peculiar symptoms.

Yale researchers have identified a new culprit — deficits in energy production within developing neurons caused by the lack of a single protein, they report Oct. 11 in the journal Cell.

Mice lacking the protein DNAJC30, which is deleted in Williams Syndrome, have functional deficits in mitochondria, the cell’s energy production machinery. These mice exhibit some of the structural abnormalities seen in Williams Syndrome patients, according to the researchers’ examination of postmortem brain tissue of patients. The function of DNAJC30 was previously unknown, but the authors now show it interacts with protein complexes that are directly necessary to make cellular energy.

The authors say the lack of energy may account for the smaller cell size, fewer dendritic spines, and thinner axons that connect neurons found in Williams patients.

This deficiency affects the overall ability of neurons to communicate with each other,” said lead author Andrew Tebbenkamp, associate research scientist in the lab of Nenad Sestan, professor of neuroscience, comparative medicine, genetics, and psychiatry.

Williams Syndrome is caused by the deletion of 28 genes on Chromosome 7 in either sperm or egg. The deletion causes the physical attributes of Williams Syndrome, including cardiovascular problems that mark the disorder. While the cardiovascular problem has been attributed to one of the 28 genes, the contributions of other genes to both patients’ intellectual disabilities or their uncanny feel for music remain murky. Deficits in DNAJC30, along with some of the other 28 genes, likely combine to produce such varied symptoms, said Tebbenkamp.

The hope is that understanding the role of mitochondrial malfunction in the disorder could lead to new ways to treat patients, he said.

Submitted by Lisa Brophy on October 11, 2018