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.
Tiranti
Valeria
V
Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, National Neurological Institute Carlo Besta, Milan, Italy.
D'Adamo
Pio
P
Briem
Egill
E
Ferrari
Gianfrancesco
G
Mineri
Rossana
R
Lamantea
Eleonora
E
Mandel
Hanna
H
Balestri
Paolo
P
Garcia-Silva
Maria-Teresa
MT
Vollmer
Brigitte
B
Rinaldo
Piero
P
Hahn
Si Houn
SH
Leonard
James
J
Rahman
Shamima
S
Dionisi-Vici
Carlo
C
Garavaglia
Barbara
B
Gasparini
Paolo
P
Zeviani
Massimo
M
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
C483228:ETHE1 protein, human; D008314:Malonates; D024101:Mitochondrial Proteins; D029543:Nucleocytoplasmic Transport Proteins; C038080:ethylmalonic acid