title: Developmental genetics of deleted mtDNA in mitochondrial oculomyopathy.
abstract: Heteroplasmic populations of mtDNA, consisting of normal mtDNA and mtDNA with large deletions, are found in the skeletal muscle and other tissues of certain patients with mitochondrial respiratory chain deficiencies, particularly in those with the CPEO (chronic progressive external ophthalmoplegia) phenotype. To study the developmental genetics of this mitochondrial disorder, the distribution of the deleted mtDNA in a wide range of tissues of different embryonic origins (total 34 samples from 27 tissues obtained at autopsy) was investigated in a patient with the CPEO syndrome. Three species of partially deleted mtDNA were observed, with deletions of 2.3 kb, 5.0 kb and 6.4 kb. Their tissue distribution suggests that the mtDNA deletions have occurred very early during embryonic development, prior to the differentiation events that lead to the formation of the three primary embryonic germ layers, and that the partially deleted mtDNA species were segregated during development mainly to the skeletal muscle and to tissues of the central nervous system.
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: S
authors.initials: S
authors.lastname: Marzuki
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: A
authors.initials: A
authors.lastname: Saifuddin Noer
authors.forename: R M
authors.initials: RM
authors.lastname: Kapsa
authors.forename: R M
authors.initials: RM
authors.lastname: Kalnins
authors.forename: E
authors.initials: E
authors.lastname: Byrne
authors.forename: T
authors.initials: T
authors.lastname: Sasmono
authors.forename: H
authors.initials: H
authors.lastname: Sudoyo
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics*; D008969:Molecular Sequence Data; D009801:Oculomotor Muscles / Q000196:embryology*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D004272:DNA, Mitochondrial