title: Site-specific deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome.
abstract: The Pearson marrow-pancreas syndrome is a fatal disorder involving the hematopoietic system and the exocrine pancreas in early infancy. We have previously shown that this disease results from a widespread defect of oxidative phosphorylation. Here, we describe deletions of the mitochondrial (mt) genome between repeated 8- to 13-bp sequences as consistent features of the disease. Studying a series of nine unrelated children, including the patient originally reported by H. Pearson, we found five different types of direct repeats at the boundaries of the mtDNA deletions and we provided evidence for conservation of the 3'-repeated sequence in the deletions. In addition, we found a certain degree of homology between the nucleotide composition of the direct repeats and several structures normally involved in mtDNA replication and mtRNA processing. These results are consistent either with the recognition and cleavage of a particular DNA sequence with a factor of still unknown origin or with a homologous recombination between direct-repeat mtDNA sequences in the Pearson syndrome.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-12, Hôpital des Enfants-Malades, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: V
authors.initials: V
authors.lastname: Cormier
authors.forename: F
authors.initials: F
authors.lastname: Koll
authors.forename: C E
authors.initials: CE
authors.lastname: Mize
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: A
authors.initials: A
authors.lastname: Veerman
authors.forename: H A
authors.initials: HA
authors.lastname: Pearson
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010182:Pancreatic Diseases / Q000150:complications / Q000235:genetics*; D010198:Pancytopenia / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D013577:Syndrome; D014617:Vacuoles
chemical_list: D004272:DNA, Mitochondrial; D012313:RNA