Mitochondrial DNA mutations in patients with orthostatic hypotension

We determined the entire sequence of the mitochondrial genome in affected i ndividuals from three families with idiopathic orthostatic hypotension. The disorder in two of these families was recently linked to chromosome arm 18 q, while the third family remains unlinked. In all three families, orthosta tic hypotension is inherited through the females, suggesting the existence of additional contributing factors, such as genomic imprinting or a mitocho ndrial modifier. We now report the presence of multiple point mutations in the mitochondrial DNA (mtDNA) in all three families. While most of the chan ges 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 posi tion 67 of the ND1 protein, and from valine to isoleucine at position 197 o f the ND2 protein. A second individual harbored a novel substitution of thr eonine with serine at position 536 of the ND5 protein. Two previously unrep orted amino acid replacements were detected in a third individual: amino ac id 193 of cytochrome b was changed from alanine to threonine, and amino aci d 88 of COIII was changed from threonine to alanine, Further studies are re quired to assess the role of these mutations in blood pressure homeostasis, (C) 1999 Wiley-Liss, Inc.