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

TitleEthylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein.
Publication TypeJournal Article
Year of Publication2004
AuthorsTiranti, V, D'Adamo, P, Briem, E, Ferrari, G, Mineri, R, Lamantea, E, Mandel, H, Balestri, P, Garcia-Silva, M-T, Vollmer, B, Rinaldo, P, Hahn, SHoun, Leonard, J, Rahman, S, Dionisi-Vici, C, Garavaglia, B, Gasparini, P, Zeviani, M
JournalAm J Hum Genet
Volume74
Issue2
Pagination239-52
Date Published2004 Feb
ISSN0002-9297
KeywordsAmino Acid Sequence, Blotting, Western, Brain Diseases, Cells, Cultured, Chromosome Mapping, Chromosomes, Human, Pair 19, Female, Fluorescent Antibody Technique, Genetic Linkage, Humans, Infant, Male, Malonates, Metabolism, Inborn Errors, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Nucleocytoplasmic Transport Proteins, Pedigree, Sequence Homology, Amino Acid
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.

DOI10.1086/381653
Alternate JournalAm. J. Hum. Genet.
Citation Key10.1086/381653
PubMed ID14732903
PubMed Central IDPMC1181922
Grant List1180 / / Telethon / Italy
TGM03Z03 / / Telethon / Italy
TGM06S01 / / Telethon / Italy