title: Mutation in the mitochondrial translation elongation factor EFTs results in severe infantile liver failure.
abstract: OBJECTIVE
  Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and often result in hepatic failure. A significant fraction of patients present mitochondrial DNA depletion but a number of cases remain unexplained. The aim of our study was to identify the disease causing gene in a kindred with intrauterine growth retardation, neonatal lactic acidosis, liver dysfunction and multiple respiratory chain deficiency in muscle.
  
  
  METHODS
  Homozygosity mapping was performed by 50K SNP genotyping and candidate genes were successively analyzed by direct sequencing on genomic DNA of the family members.
  
  
  RESULTS
  SNP genotyping detected several regions of homozygosity in which we focused our attention to genes involved in mitochondrial translation. We sequenced the TSFM gene, encoding the mitochondrial translation factor EFTs and identified a homozygous mutation changing a highly conserved arginine into a tryptophan (R312W).
  
  
  CONCLUSIONS
  This mutation has been previously reported in two unrelated kindred presenting two distinct syndromes (fatal mitochondrial encephalomyopathy and hypertrophic cardiomyopathy respectively). The description of a third syndrome associated with a same TSFM mutation gives support to the broad clinical and genetic heterogeneity of mitochondrial translation deficiencies in human. It suggests that mitochondrial translation deficiency represents a growing cause of hepatic failure of mitochondrial origin in infants.
authors: Department of Genetics, Hôpital Necker-Enfants Malades, Université Paris Descartes and INSERM U781, 149 rue de Sèvres, 75015 Paris, France.
authors: Vanessa
authors: V
authors: Vedrenne
authors: Louise
authors: L
authors: Galmiche
authors: Dominique
authors: D
authors: Chretien
authors: Pascale
authors: P
authors: de Lonlay
authors: Arnold
authors: A
authors: Munnich
authors: Agnès
authors: A
authors: Rötig
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017114:Liver Failure, Acute / Q000209:etiology / Q000235:genetics*; D008297:Male; D028361:Mitochondrial Diseases / Q000209:etiology / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D010445:Peptide Elongation Factors / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D010445:Peptide Elongation Factors; C023512:elongation factor Ts