title: Mitochondrial DNA mutations in patients with orthostatic hypotension.
abstract: We determined the entire sequence of the mitochondrial genome in affected individuals from three families with idiopathic orthostatic hypotension. The disorder in two of these families was recently linked to chromosome arm 18q, while the third family remains unlinked. In all three families, orthostatic hypotension is inherited through the females, suggesting the existence of additional contributing factors, such as genomic imprinting or a mitochondrial modifier. We now report the presence of multiple point mutations in the mitochondrial DNA (mtDNA) in all three families. While most of the changes are common polymorphisms, several novel mutations were found that merit further consideration. In one individual, we detected a T-to-C transition at position 1243 in the 12SrRNA, a change from threonine to alanine at position 67 of the ND1 protein, and from valine to isoleucine at position 197 of the ND2 protein. A second individual harbored a novel substitution of threonine with serine at position 536 of the ND5 protein. Two previously unreported amino acid replacements were detected in a third individual: amino acid 193 of cytochrome b was changed from alanine to threonine, and amino acid 88 of COIII was changed from threonine to alanine. Further studies are required to assess the role of these mutations in blood pressure homeostasis.
authors.affiliation: Department of Medicine, Hypertension Section, Boston University School of Medicine, Boston, Massachusetts 02118, USA. fschw@bu.edu
authors.forename: F
authors.initials: F
authors.lastname: Schwartz
authors.forename: C T
authors.initials: CT
authors.lastname: Baldwin
authors.forename: J
authors.initials: J
authors.lastname: Baima
authors.forename: H
authors.initials: H
authors.lastname: Gavras
mesh_terms: D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial