This report describes encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1); EMPF1 is associated with both autosomal dominant and autosomal recessive inheritance. The human gene implicated in this disease is DNM1L, which encodes dynamin-1-like protein. This protein belongs to the dynamin family of large GTPases that mediate membrane remodeling during a variety of cellular processes; DNM1L has an important role in the fission of mitochondria and peroxisomes. There is a single orthologous gene in Drosophila, Drp1, for which loss-of-function alleles, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
Multiple UAS alleles of the human Hsap\DNM1L gene have been introduced into flies, including wild-type and variants implicated in DNM1L. Heterologous rescue (functional complementation) has been demonstrated. Variant(s) implicated in human disease tested (as transgenic human gene, DNM1L): the A395D, G350R, E379K, and Y691C variant forms of the human gene have been introduced into flies. Variants were tested for ability to rescue the phenotypes of Drp1 loss-of-function mutations.
Homozygous loss-of-function mutations of Dmel\Drp1 are lethal, typically in the larval stage, with defects in mitochondrial trafficking to synapses, mitochondrial morphology, and synaptic transmission. Genetic and physical interactions of Dmel\Drp1 have been described; see below and in the Drp1 gene report.
[updated Oct. 2019 by FlyBase; FBrf0222196]
[ENCEPHALOPATHY DUE TO DEFECTIVE MITOCHONDRIAL AND PEROXISOMAL FISSION 1; EMPF1](https://omim.org/entry/614388)
[DYNAMIN 1-LIKE; DNM1L](https://omim.org/entry/603850)
Encephalopathy due to defective mitochondrial and peroxisomal fission-1 is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline. The age at onset, features, and severity are variable, and some patients may not have clinical evidence of mitochondrial or peroxisomal dysfunction (summary by Sheffer et al., 2016, pubmed:26992161; Fahrner et al., 2016, pubmed:27145208). [from OMIM:614388; 2017.09.14]
DNM1L encodes the dynamin-1-like protein, which belongs to the dynamin family of large GTPases that mediate membrane remodeling during a variety of cellular processes. DNM1L has an important role in the fission of mitochondria and peroxisomes (summary by Pitts et al., 2004; pubmed:15364948). [from OMIM:614388, OMIM:603850; 2017.09.14]