Scientists unravel genetic mystery of rare neurodevelopmental disorder, providing definitive diagnoses for 21 families worldwide

Newswise – ROCHESTER, MN – A collaborative team of scientists led by the Mayo Clinic Individual Medicine Center He discovered 15 additional genetic mutations in the KCNK9 gene that cause 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 change in the KCNK9 gene was known to cause the disorder, called KCNK9 . Imprint Syndrome. Our study describes 15 new genetic modifications,” says Ph.D. Margot Cousin, a translational genomics researcher at the Mayo Clinic. Individual Medicine Center and lead author of the study.

Through the new study published in Genomics, 21 families with a genetic variant in KCNK9 received a definitive genetic diagnosis. While there is no specific treatment available for KCNK9 fingerprint 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,” says Dr.

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

A pathogenic variant in the KCNK9 gene alters the TASK3 protein channel, disrupting the normal development of neurons. When the TASK3 protein channel functions properly, it maintains the cell’s ability to generate electrical signals and regulate cell activity.

For the study, Dr. Cousin and her team analyzed genetic variants and disease symptoms, including unique facial features, of 47 people with mutations in KCNK9 associated with KCNK9 imprinting syndrome. Study participants were recruited from hospitals or clinics from the United States, the United Kingdom, Germany, Italy, France, the Netherlands, Canada and Singapore.

“We next determined the effects of the genetic variants on the protein encoded by the KCNK9 gene, the TASK3 potassium channel. To do this, we used computer-based as well as cell-based methods to measure changes in how the TASK3 channel functions as a consequence of each variant,” explains Dr. Cousin. “We were able to show that these gene mutations have diverse effects on the current through the TASK3 channel, but most of them change how the channel protein is regulated by the body.”

Dr. Cousin says advances in genome sequencing and the ability to interpret the vast amounts of data generated using multiscale techniques are accelerating the discovery of disease-causing genes. Omics technologies include gene discovery and genomics; RNA messenger, transcription; Proteins and proteins. Metabolites, Metabolites.

“Not so long ago, the discovery of a single genetic variant was hailed as a milestone,” says Dr. Kosin. “We are now able to shed light on a spectrum of epigenetic changes in the gene to fully understand the exact mechanisms of the disease.”

Dr. Cousin stresses that with the widespread use of genetic technologies in clinical care, identifying genetic variation is no longer a bottleneck.

“The challenge that remains is to identify individuals who have genetic variations and similar disease manifestations and then solve the mechanism by which these genetic changes cause disease through multidisciplinary expertise,” says Dr. Kosin.

The study was carried out through a collaboration between researchers from Mayo Clinic and the Medical College of Wisconsin, as well as the University of Kent and the University of Greenwich in the United Kingdom.

This study was supported by the German Research Foundation, the Mayo Clinic Center for Individualized Medicine, and the Linda T. Wisconsin Scholarship Fund.

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