Moreover, the uncertainty about the pathological significance of the variants in TBX4 and KCNK3 hampers any robust interpretation. Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, et al. Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons.
KCNK3 (alias Task-1) was found to be mutated after initial exome sequencing in an unresolved case of familial PAH and subsequent investigations of familial and idiopathic PAH.
This study confirms the younger age at onset in hereditary PAH, in particular in individuals who are BMPR2 mutations carriers.
Unfortunately, the clinical and hemodynamic parameters were not available during the follow-up period. Eyries M, Montani D, Girerd B, Perret C, Leroy A, Lonjou C, et al.
This observation is really unique and should spur extensive clinical and pharmacological investigation of the patient in order to better understand the role of the channel in PAH.
In mice, biallelic disruption of the Task-1 gene is not lethal because Task-3 subunits compensate for the absence of the Task-1 subunit.