title: Identical mitochondrial DNA deletion in a woman with ocular myopathy and in her son with pearson syndrome.
abstract: Single deletions of mitochondrial DNA (mtDNA) are associated with three major clinical conditions: Kearns-Sayre syndrome, a multisystem disorder; Pearson syndrome (PS), a disorder of the hematopoietic system; and progressive external ophthalmoplegia (PEO), primarily affecting the ocular muscles. Typically, single mtDNA deletions are sporadic events, since the mothers, siblings, and offspring of affected individuals are unaffected. We studied a woman who presented with PEO, ptosis, and weakness of pharyngeal, facial, neck, and limb muscles. She had two unaffected children, but another of her children, an infant son, had sideroblastic anemia, was diagnosed with PS, and died at age 1 year. Morphological analysis of a muscle biopsy sample from the mother showed cytochrome c oxidase-negative ragged-red fibers-a typical pattern in patients with mtDNA deletions. Southern blot analysis using multiple restriction endonucleases and probed with multiple mtDNA fragments showed that both the mother and her infant son harbored an identical 5,355-bp single deletion in mtDNA, without flanking direct repeats. The deletion was the only abnormal species of mtDNA identified in both patients, and there was no evidence for duplications. We conclude that, although the vast majority of single large-scale deletions in mtDNA are sporadic, in rare cases, single deletions can be transmitted through the germline.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Yingying
authors.initials: Y
authors.lastname: Tang
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishigaki
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sue
authors.forename: Sindu
authors.initials: S
authors.lastname: Krishna
authors.forename: Jose R
authors.initials: JR
authors.lastname: Carlo
authors.forename: Judith
authors.initials: J
authors.lastname: Willner
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D005128:Eye Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics*; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial