Neurological symptoms, including epilepsy, occur quite commonly in mitochondrial disorders. This report describes work done with the fly gene tko, which encodes the mitochondrial small ribosomal protein S12; the orthologous gene in human is MRPS12. Classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\tko.
A UAS construct of the wild-type human Hsap\MRPS12 gene has been introduced into flies, but has not been characterized. To date, this gene has not been reported as implicated in a mitochondrial or epilepsy-related disorder by OMIM (MIM:603021).
Mutations in a number of Drosophila genes, including Dmel\tko, produce phenotypes of seizure sensitivity, including a lowered threshold to evoked electrophysiologically recorded seizure-like activity and "bang-sensitive" phenotypes.
Animals homozygous for amorphic mutations of Dmel\tko die before the end of the larval stage. Less severe mutations allow survival to adulthood, with adults exhibiting developmental delay, reduced lifespan, a seizure-sensitive phenotype (bang sensitivity), impaired male courtship, and defective response to sound. A small number of genetic interactions have been described for Dmel\tko; see the tko gene report.
A recent study has shown that modification of the dietary medium can significantly impact the severity of the tko seizure-sensitive phenotypes.
[updated Apr. 2020 by FlyBase; FBrf0222196]
Neurological disorders, including epilepsy, occur quite commonly in mitochondrial disorders. Most of the epilepsy caused by a mitochondrial disorder starts in childhood and usually in the first 2 years of life (https://www.epilepsy.org.uk/info/syndromes/mitochondrial-disorders).
Hearing impairment is common in patients with mitochondrial disorders, affecting over half of all cases at some time in the course of the disease. In some patients, deafness is only part of a multisystem disorder (Scarpelli et al., 2012; pubmed:22567382).
One to one (1 human to 1 Drosophila).
Ortholog of human MRPS12 (1 Drosophila to 1 human). Dmel\tko shares 56% identity and 64% similarity with human MRPS12.
