• developmental and epileptic encephalopathy 87

This report describes developmental and epileptic encephalopathy 87 (DEE87), previously called epileptic encephalopathy, early infantile, 87 (EIEE87); DEE87 exhibits autosomal dominant inheritance. The gene implicated in this disease is CDK19, which encodes one of the components of the Mediator co-activator complex and thus has a role in transcriptional regulation. There is a single orthologous gene in Drosophila, Cdk8, for which for which a classical loss-of-function allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Cdk8 is also orthologous to a second human gene, CDK8.

UAS constructs of the human Hsap\CDK19 gene have been introduced into flies, including wild-type and variants implicated in human disease. Heterologous rescue (functional complementation) has been demonstrated for the larval lethal phenotype. Variant(s) implicated in human disease tested (as transgenic human gene, CDK19): the T196A and Y32H variant forms of the human gene have been introduced into flies.

Animal homozygous for loss-of-function alleles of Dmel\Cdk8 typically die before the end of the larval stage. Homozygous larvae have a significantly increased triglyceride content compared to controls. Pan-neuronal RNAi-mediated knockdown of Cdk8 results in semi-lethality; the few eclosing flies exhibit severe seizures and a reduced lifespan. Genetic and physical interactions have been described for Dmel\Cdk8; see below and in the Cdk8 gene report.

Results in Drosophila indicate that Dmel\Cdk8 may function in regulating lipid homeostasis (FBrf0218723). Genes encoding other components of the Mediator complex have been implicated in susceptibility to obesity; see FBhh0000506 and FBhh0000507.

[updated Feb. 2021 by FlyBase; FBrf0222196]