医疗专业人员

Aug. 25, 2022

An international scientific team led by the Mayo Clinic Center for Individualized Medicine has discovered 15 additional genetic alterations associated with KCNK9 imprinting syndrome. Previously, only one genetic alteration was known to cause this rare neurodevelopmental syndrome.

The study, published in the June 13, 2022, edition of Genome Medicine, confirms that nine of the 15 newly reported variants cause the disease. Symptoms of the disorder include speech and motor impairment, behavioral abnormalities, intellectual disability, and distinctive facial features.

The researchers analyzed the genetic variants and disease symptoms of 47 individuals with genetic alterations in the KCNK9 gene associated with KCNK9 imprinting syndrome. The researchers then determined the effects of the mutations on the TASK3 potassium channel protein, which is encoded by the KCNK9 gene. Alterations in the TASK3 channel disrupt normal neuron development and function.

Key points:

• The researchers found that the 15 genetic mutations have varied effects on the current that travels through the TASK3 channel
• Most of the variants altered how the channel protein is regulated
• The researchers identified a novel hotspot for de novo variants — at amino acid Arg131 of the protein — that is more common than the previously identified Gly236 hot spot

The researchers note that identifying the root cause of the syndrome is the key step toward finding a cure.

For more information

Cousin MA, et al. Gain and loss of TASK3 channel function and its regulation by novel variation cause KCKN9 imprinting syndrome. Genome Medicine. 2022;14:62.

Refer a patient to Mayo Clinic.