AUTOSOMAL-DOMINANT ORTHOSTATIC HYPOTENSIVE DISORDER MAPS TO CHROMOSOME 18Q

Familial orthostatic hypotensive disorder is characterized by light-he adedness on standing, which may worsen to syncope, palpitations, and b lue-purple ankle discoloration, and is accompanied by a marked decreas e in systolic blood pressure, an increase in diastolic pressure, and t achycardia, all of which resolve when supine. We ascertained three fam ilies in which this disorder is inherited as an autosomal dominant tra it with reduced penetrance. A genomewide scan was conducted in the two largest families, and three regions with multipoint LOD scores >1.5 w ere identified. Follow-up of these regions with additional markers in all three families yielded significant evidence of linkage at chromoso me 18q. A maximum multipoint LOD score of 3.21 in the three families w as observed at D18S1367, although the smallest family had negative LOD scores in the entire region. There was significant evidence of linkag e in the presence of heterogeneity at 18q, with a maximum LOD score of 3.92 at D18S1367 in the two linked families. Identification of the ge ne responsible for orthostatic hypotensive disorder in these families may advance understanding of the general regulatory pathways involved in the continuum, from hypotension to hypertension, of blood pressure.