Familial orthostatic tachycardia.
OBJECTIVE
Postural tachycardia syndrome is an autonomic disorder primarily of younger women. The patient population is heterogeneous, making diagnosis and treatment a challenge. A mutation in the norepinephrine (noradrenaline) transporter gene prompted further genetic analysis.


RESULTS
Eleven new mutations were found in the human norepinephrine transporter gene, although none were directly associated with postural tachycardia syndrome. The 5'-flanking -1012C --> T variant of the dopamine beta-hydroxylase gene was slightly increased and protection was associated with a reduced incidence of two mutations in the endothelial nitric oxide synthase gene, and one in endothelin-1. Mutations in other disease-related genes suggest a potential relationship with the pathogenesis of postural tachycardia syndrome. Benign joint hypermobility syndrome, for example, shares similar autonomic symptoms and is linked to a mutation in tenascin-X. Additional genetic findings are discussed as potential contributors to vascular health and neurodegeneration.


CONCLUSIONS
Genetic testing can reveal molecular mechanisms of disease and provide an additional strategy for diagnosis and treatment of heterogeneous patient populations such as postural tachycardia syndrome. It is quite likely that the pathogenesis of this disorder will be attributed to numerous genetic mutations, both subtle and overt. Therefore, continued study of the relationships between genotype and phenotype are necessary to better understand this syndrome and others with associated dysautonomia.
Keller
Nancy R
NR
Autonomic Dysfunction Center, Division of Clinical Pharmacology, Departments of Medicine, Pharmacology and Neurology, Tennessee, USA.
Robertson
David
D
D001342:Autonomic Nervous System Diseases / Q000235:genetics*; D002199:Capillary Permeability / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011187:Posture; D011978:Receptors, Nicotinic / Q000235:genetics; D013577:Syndrome; D013610:Tachycardia / Q000235:genetics*; D014661:Vasoconstriction / Q000235:genetics
D050484:Norepinephrine Plasma Membrane Transport Proteins; D011978:Receptors, Nicotinic; D004299:Dopamine beta-Hydroxylase