This report describes MEPAN syndrome, also known as dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (DYTOABG); MEPAN syndrome exhibits autosomal recessive inheritance. The human gene implicated in this disease is mitochondrial enoyl coenzyme A reductase (MECR), an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFAS). There is a single Drosophila ortholog, Mecr, for which a small number of genetic reagents have been generated, including loss-of-function alleles and RNAi targeting constructs.
UAS constructs of the human Hsap\MECR gene has been introduced into flies, including wild-type and constructs carrying variants implicated in this disease; see the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) is observed tor the Dmel\Mecr loss-of-function lethal phenotype.
Loss of function of Drosophila Mecr causes lethality in the larval stage; neuronal loss of Mecr results in progressive neurodegeneration. In flies lacking functional Mecr a defect in Fe-S cluster biogenesis is observed; increased iron levels are also observed, leading to elevated ceramide levels. Reducing the levels of either iron or ceramide suppresses the neurodegenerative phenotypes. These data suggest that the ceramides and iron metabolomic defects are connected and that MECR plays a central role in maintaining homeostasis between these pathways by regulating mtFAS.
[updated Nov. 2023 by FlyBase; FBrf0222196]
Dystonia describes a neurologic condition characterized by involuntary, sustained muscle contractions affecting one or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in some types of dystonia. Dystonia has been classified as primary (dystonia as the sole or major symptom) or secondary (a symptom of another disorder), and by age of onset, muscle groups affected, and mode of inheritance (Muller and Kupke, 1990, pubmed:2404852; Nemeth, 2002, pubmed:11912106). [from MIM:128100; 15.07.07]
Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonias are classified by several clinical characteristics including age of onset (infancy (birth to 2 years), childhood (3-12 years), adolescence (13-20 years), early adulthood (21-40 years), and late adulthood (over 40 years)), temporal pattern (static or progressive disease course and the variability of symptoms, which may persist, fluctuate diurnally or occur only with specific actions or in paroxysms), by body distribution, which is divided into focal (affecting a single body part), segmental (affecting two or more contiguous muscle groups, multifocal (affecting two or more non-contiguous muscle groups), hemidystonia (affecting an arm and a leg on one side of the body), or generalized (affecting the trunk and two or more other sites), and by coexistence of other movement disorders. (Balint and Bhatia, 2014, PMID:24978640, Gene_reviews, Dystonia Overview, 2015.07.09)
[DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES; DYTOABG](https://omim.org/entry/617282)
[MITOCHONDRIAL TRANS-2-ENOYL-CoA REDUCTASE; MECR](https://omim.org/entry/608205)
Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; also known as MEPAN syndrome) is an autosomal recessive neurologic disorder characterized by onset of involuntary movements in the first decade of life. Optic atrophy develops around the same time or slightly later. Severity is variable, and some patients lose independent ambulation. Brain imaging shows abnormalities in the basal ganglia. Cognition appears to be unaffected (summary by Heimer et al., 2016; pubmed:27817865). [from MIM:617282; 2023.11.14]
Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (MEPAN syndrome) is caused by homozygous or compound heterozygous mutation in the MECR gene. [from MIM:617282; 2023.11.14]
MECR encodes mitochondrial trans-2-enoyl-CoA reductase, an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis. [GeneCards, MECR: 2023.11.14]
One to one: 1 human gene to 1 Drosophila gene; multiple related genes in both species.
High-scoring ortholog of human MECR (1 Drosophila to 1 human; multiple related genes in both species.)
