Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome.
Margot A CousinEmma L VealeNikita R DsouzaSwarnendu TripathiRobyn G HoldenMaria ArelinGeoffrey BeekMir Reza BekheirniaJasmin BeygoVikas BhambhaniMartin BialerStefania BigoniCyrus BoelmanJenny CarmichaelThomas CourtinBenjamin CogneIvana DabajDiane DoummarLaura FazilleauAlessandra FerliniRalitza H GavrilovaJohn M GrahamTobias B HaackJane JuusolaSarina G KantSaima KayaniBoris KerenPetra KettelerChiara KlöcknerTamara T KoopmannTeresa M KruisselbrinkAlma KuechlerLaëtitia LambertXénia LatypovaRobert Roger LebelMagalie S LeducEmanuela LeonardiAndrea M LewisWendy LiewKeren MacholSamir MardiniKirsty McWalterCyril MignotJulie McLaughlinAlessandra MurgiaVinodh NarayananCaroline NavaSonja NeuserMathilde NizonDavide OgnibeneJoohyun ParkKonrad PlatzerCéline PoirsierMaximilian RadtkeKeri RamseyCassandra K RunkeMaria J Guillen SacotoFernando ScagliaMarwan ShinawiStephanie SprangerEe Shien TanJohn TaylorAnne-Sophie TrentesauxFilippo VairoRebecca WillaertNeda ZadehRaul UrrutiaDusica Babovic-VuksanovicMichael T ZimmermannAlistair A MathieEric W KleePublished in: Genome medicine (2022)
This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation.