Scientists unravel genetic mystery of rare neurodevelopmental disorder, provide definitive diagnoses to 21 families worldwide

A collaborative team of scientists led by Mayo Clinic’s Center for Individualized Medicine has discovered 15 additional genetic mutations in the KCNK9 gene that cause a neurodevelopmental syndrome. Symptoms of the disorder range from speech and motor impairment to behavioral abnormalities, intellectual disability and distinctive facial features.

“Until now, only one genetic alteration in the KCNK9gene was known to cause the disorder, called KCNK9 imprinting syndrome. Our study describes 15 new genetic alterations,” says Margot Cousin, Ph.D., a translational genomics researcher in Mayo Clinic’s Center for Individualized Medicine and the study’s lead author.

Through the new study, which is published in Genome Medicine, 21 families with a genetic variant in KCNK9 received a definitive genetic diagnosis. While no specific treatment is available for KCNK9 imprinting syndrome, Dr. Cousin says her team’s discovery could guide therapeutic development.

“We can now provide more patients with an answer to the root cause of their disease, which is the most important first step toward finding a cure,” Dr. Cousin says.

The KCNK9 gene provides instructions for making a specialized transport protein called TASK3, which regulates the activity of neurons in the brain. The KCNK9 imprinting syndrome occurs when there is a mutation in the copy of the gene inherited from the mother. The gene from the father is always silenced.

A pathogenic variant in the KCNK9 gene alters the TASK3 protein channel, which disrupts normal neuron development. When the TASK3 protein channel is functioning properly, it maintains the cell’s ability to generate electrical signals and regulate the activity of cells.

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