title: Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy.
abstract: BACKGROUND
  The ANT1 gene, encoding ADP/ATP translocase 1, was investigated in an adult patient with an autosomal recessive mitochondrial disorder characterised by congenital cataracts, hypertrophic cardiomyopathy, myopathy and lactic acidosis.
  
  
  RESULTS
  ANT1 sequencing showed that the patient was homozygous for a new nucleotide variation, c.111+1G→A, abolishing the invariant GT splice donor site of intron 1. The ANT1 transcript was undetectable in both muscle and skin fibroblasts. A markedly abnormal metabolic profile was found, and skeletal muscle showed a dramatic proliferation of abnormal mitochondria, increased mitochondrial mass, and multiple mitochondrial DNA deletions. No compensating increase in the transcript level of the ANT3 gene, which encodes the human ubiquitous isoform of the ADP/ATP translocase, was observed. The patient's heterozygous mother had normal clinical, biochemical and pathological features.
  
  
  CONCLUSIONS
  Complete loss of expression of the ANT1 gene causes a clinical syndrome mainly characterised by cardiomyopathy and myopathy. This report expands the clinical spectrum of ANT1-related human diseases, and emphasises the crucial role of the mitochondrial ADP/ATP carriers in muscle function and pathophysiology of human myopathies.
authors.affiliation: Département de Neurologie, Hôpitaux Universitaires, Strasbourg cedex, France. andoni.echaniz-laguna@chru-strasbourg.fr
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: Maïté
authors.initials: M
authors.lastname: Chassagne
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ceresuela
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouvet
authors.forename: Sylvie
authors.initials: S
authors.lastname: Padet
authors.forename: Cécile
authors.initials: C
authors.lastname: Acquaviva
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vinzio
authors.forename: Dominique
authors.initials: D
authors.lastname: Bozon
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mousson de Camaret
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics*; D033781:Adenine Nucleotide Translocator 3 / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D008279:Magnetic Resonance Imaging; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D059906:Neuroimaging; D010375:Pedigree; D055815:Young Adult
chemical_list: D033741:Adenine Nucleotide Translocator 1; D033781:Adenine Nucleotide Translocator 3; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human