Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.

ABSTRACT:

Background

Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood.

Methods

This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein mod

SUBMITTER: Cousin MA 

PROVIDER: S-EPMC9195326 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature