Lethal digenic mutations in the K⁺ channels Kir4.1 (KCNJ10) and SLACK (KCNT1) associated with severe-disabling seizures and neurodevelopmental delay.

ABSTRACT: A 2-yr-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia, and tonic-clonic seizures that caused the death of the patient. Targeted and whole exome sequencing revealed two heterozygous missense variants: a novel mutation in the KCNJ10 gene that encodes for the inward-rectifying K⁺ channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na⁺-activated K⁺ channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4.1 mutation. The mutant and wild-type KCNJ10 constructs were generated and heterologously expressed in Xenopus laev

SUBMITTER: Hasan S 

PROVIDER: S-EPMC5646198 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature