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Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein

Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein
Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein
Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels. High levels of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase activity is decreased in skeletal muscle. By use of a combination of homozygosity mapping, integration of physical and functional genomic data sets, and mutational screening, we identified GenBank D83198 as the gene responsible for EE. We also demonstrated that the D83198 protein product is targeted to mitochondria and internalized into the matrix after energy-dependent cleavage of a short leader peptide. The gene had previously been known as "HSCO" (for hepatoma subtracted clone one). However, given its role in EE, the name of the gene has been changed to "ETHE1." The severe consequences of its malfunctioning indicate an important role of the ETHE1 gene product in mitochondrial homeostasis and energy metabolism.
0002-9297
239-252
Tiranti, Valeria
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D'Adamo, Pio
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Briem, Egill
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Ferrari, Gianfrancesco
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Mineri, Rossana
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Lamantea, Eleonora
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Mandel, Hanna
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Balestri, Paolo
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Garcia-Silva, Maria-Teresa
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Rinaldo, Piero
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Hahn, Si Houn
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Leonard, James
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Rahman, Shamima
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Dionisi-Vici, Carlo
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Garavaglia, Barbara
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Gasparini, Paolo
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Zeviani, Massimo
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Tiranti, Valeria
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D'Adamo, Pio
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Briem, Egill
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Ferrari, Gianfrancesco
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Mineri, Rossana
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Lamantea, Eleonora
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Mandel, Hanna
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Balestri, Paolo
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Garcia-Silva, Maria-Teresa
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Rinaldo, Piero
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Hahn, Si Houn
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Leonard, James
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Rahman, Shamima
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Dionisi-Vici, Carlo
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Garavaglia, Barbara
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Gasparini, Paolo
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Zeviani, Massimo
ed5aa7ee-62bd-4cde-9429-97e503319a17

Tiranti, Valeria, D'Adamo, Pio, Briem, Egill, Ferrari, Gianfrancesco, Mineri, Rossana, Lamantea, Eleonora, Mandel, Hanna, Balestri, Paolo, Garcia-Silva, Maria-Teresa, Rinaldo, Piero, Hahn, Si Houn, Leonard, James, Rahman, Shamima, Dionisi-Vici, Carlo, Garavaglia, Barbara, Gasparini, Paolo and Zeviani, Massimo (2004) Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. The American Journal of Human Genetics, 74 (2), 239-252. (doi:10.1086/381653). (PMID:10556302)

Record type: Article

Abstract

Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels. High levels of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase activity is decreased in skeletal muscle. By use of a combination of homozygosity mapping, integration of physical and functional genomic data sets, and mutational screening, we identified GenBank D83198 as the gene responsible for EE. We also demonstrated that the D83198 protein product is targeted to mitochondria and internalized into the matrix after energy-dependent cleavage of a short leader peptide. The gene had previously been known as "HSCO" (for hepatoma subtracted clone one). However, given its role in EE, the name of the gene has been changed to "ETHE1." The severe consequences of its malfunctioning indicate an important role of the ETHE1 gene product in mitochondrial homeostasis and energy metabolism.

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Accepted/In Press date: 17 November 2003
Published date: February 2004

Identifiers

Local EPrints ID: 189521
URI: https://eprints.soton.ac.uk/id/eprint/189521
ISSN: 0002-9297
PURE UUID: e66ac994-ff0c-49cb-abe0-98053341be9b

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Date deposited: 02 Jun 2011 13:14
Last modified: 21 Aug 2017 16:32

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Contributors

Author: Valeria Tiranti
Author: Pio D'Adamo
Author: Egill Briem
Author: Gianfrancesco Ferrari
Author: Rossana Mineri
Author: Eleonora Lamantea
Author: Hanna Mandel
Author: Paolo Balestri
Author: Maria-Teresa Garcia-Silva
Author: Piero Rinaldo
Author: Si Houn Hahn
Author: James Leonard
Author: Shamima Rahman
Author: Carlo Dionisi-Vici
Author: Barbara Garavaglia
Author: Paolo Gasparini
Author: Massimo Zeviani

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