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General Information
Name
encephalopathy due to defective mitochondrial and peroxisomal fission 1
FlyBase ID
FBhh0000619
Overview

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]

Disease Summary Information
Disease Summary: encephalopathy due to defective mitochondrial and peroxisomal fission 1
OMIM report

[ENCEPHALOPATHY DUE TO DEFECTIVE MITOCHONDRIAL AND PEROXISOMAL FISSION 1; EMPF1](https://omim.org/entry/614388)

Human gene(s) implicated

[DYNAMIN 1-LIKE; DNM1L](https://omim.org/entry/603850)

Symptoms and phenotype

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]

Genetics

Encephalopathy due to defective mitochondrial and peroxisomal fission-1 (EMPF1) can be caused by heterozygous mutation in the DNM1L gene; autosomal recessive inheritance has been observed in some pedigrees. [from OMIM:614388; 2017.09.14]

Cellular phenotype and pathology
Molecular information

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]

External links
Disease synonyms
infantile encephalopathy
EMPF1
encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Dynamin related protein 1 (Drp1) encodes a dynamin-like GTPase that mediates mitochondrial fission through a process that involves translocation to the mitochondrial outer membrane and oligomerization. It is required for normal neuronal development and maintenance of postmitotic neuronal function and viability. [Date last reviewed: 2018-09-27]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human DNM1L (1 Drosophila to 1 human). Dmel\Drp1 shares 63% identity and 76% similarity with the human gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (1 groups)
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (13 alleles)
    Models Based on Experimental Evidence ( 1 )
    Modifiers Based on Experimental Evidence ( 8 )
    Models Based on Experimental Evidence ( 4 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    References (7)