title: Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein.
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.
authors.affiliation: Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, National Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
authors.forename: Pio
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Egill
authors.initials: E
authors.lastname: Briem
authors.forename: Gianfrancesco
authors.initials: G
authors.lastname: Ferrari
authors.forename: Rossana
authors.initials: R
authors.lastname: Mineri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: Paolo
authors.initials: P
authors.lastname: Balestri
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Garcia-Silva
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmer
authors.forename: Piero
authors.initials: P
authors.lastname: Rinaldo
authors.forename: Si Houn
authors.initials: SH
authors.lastname: Hahn
authors.forename: James
authors.initials: J
authors.lastname: Leonard
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D001927:Brain Diseases / Q000235:genetics*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005260:Female; D005455:Fluorescent Antibody Technique; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D008314:Malonates / Q000378:metabolism*; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D029543:Nucleocytoplasmic Transport Proteins; D010375:Pedigree; D017386:Sequence Homology, Amino Acid
chemical_list: C483228:ETHE1 protein, human; D008314:Malonates; D024101:Mitochondrial Proteins; D029543:Nucleocytoplasmic Transport Proteins; C038080:ethylmalonic acid