This report describes Charcot-Marie-Tooth disease, axonal, type 2EE, an autosomal recessive subtype of Charcot-Marie-Tooth disease. The human gene implicated is MPV17, which encodes a mitochondrial inner membrane protein involved in mitochondrial deoxynuclueotide homeostasis and maintenance of mitochondrial DNA. There is one high-scoring Drosophila ortholog, Dmel\Mpv17, for which RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. MPV17 has also been been implicated in mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (MIM:256810, FBhh0001498).
A tagged wild-type UAS construct of the human gene, Hsap\MPV17 has been introduced into flies.
Pan-neuronal RNAi-mediated targeted knockdown of Dmel\Mpv17 results in deficits in learning and locomotive behavior, impairs mitochondrial function in the larval CNS, and induces abnormal morphology in the larval neuromuscular junction.
[updated Nov. 2022 by FlyBase; FBrf0222196]
Charcot-Marie-Tooth disease (CMT) constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. CMT is divided into several major types: Type 1 is characterized by demyelination and by a significantly slowed motor median nerve conduction velocity (NCV). Type 2 is characterized by axonal abnormalities and a normal or slightly reduced NCV. "Intermediate" types describe CMT families with nerve conduction velocities, in different affected individuals, that overlap the division between Type 1 and Type 2. Additional types are defined on the basis inheritance patterns. [from MIM:609260 and MIM:606482; 2015.12.15]
Symptoms typically include progressive distal muscle weakness and atrophy, often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet. [from Gene Reviews, http://www.ncbi.nlm.nih.gov/books/NBK1358 2015.12.15]
[CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE; CMT2EE](https://omim.org/entry/618400)
[MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17](https://omim.org/entry/137960)
Charcot-Marie-Tooth disease type 2EE (CMT2EE) is an autosomal recessive sensorimotor peripheral axonal neuropathy with onset in the first or second decades of life. The disorder primarily affects the lower limbs and is slowly progressive, sometimes resulting in loss of ambulation, with later onset of upper limb involvement. There is significant distal muscle weakness and atrophy, usually with foot or hand deformities. Skeletal muscle biopsy shows findings of disturbed mitochondrial maintenance. Cognition is unaffected, and chronic liver disease is absent (summary by Baumann et al., 2019, pubmed:30298599). [from MIM:618400; 2023.02.23]
CMT2EE is caused by homozygous or compound heterozygous mutation in the MPV17 gene on chromosome 2p23. [from MIM:618400; 2023.02.23]
Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress, and is involved in mitochondrial homeostasis (Antonenkov, et al., 2015, pubmed:25861990). Involved in mitochondrial deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial DNA (mtDNA) maintenance (Dalla Rosa, et al., 2016, pubmed:26760297). May be involved in the regulation of reactive oxygen species metabolism and the control of oxidative phosphorylation. [from Uniprot:P39210; 2023.02.22]
The MPV17 gene encodes a mitochondrial inner membrane protein that is involved in mitochondrial deoxynucleotide homeostasis and maintenance of mtDNA (summary by Baumann et al., 2019). [from MIM:137960; 2023.02.23]
One to one (1 human to 1 Drosophila); MPV17 has one high-scoring Drosophila ortholog, Mpv17.
High-scoring ortholog of human MPV17(1 Drosophila to 1 human).
