DeStefano A L, Baldwin C T, Burzstyn M, Gavras I, Handy D E, Joost O, Martel T, Nicolaou M, Schwartz F, Streeten D H, Farrer L A, Gavras H
Department of Neurology, Center for Human Genetics, Boston University School of Medicine, Boston, MA 02118, USA.
Am J Hum Genet. 1998 Nov;63(5):1425-30. doi: 10.1086/302096.
Familial orthostatic hypotensive disorder is characterized by light-headedness on standing, which may worsen to syncope, palpitations, and blue-purple ankle discoloration, and is accompanied by a marked decrease in systolic blood pressure, an increase in diastolic pressure, and tachycardia, all of which resolve when supine. We ascertained three families in which this disorder is inherited as an autosomal dominant trait with reduced penetrance. A genomewide scan was conducted in the two largest families, and three regions with multipoint LOD scores >1.5 were identified. Follow-up of these regions with additional markers in all three families yielded significant evidence of linkage at chromosome 18q. A maximum multipoint LOD score of 3.21 in the three families was observed at D18S1367, although the smallest family had negative LOD scores in the entire region. There was significant evidence of linkage 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 gene 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.
家族性直立性低血压障碍的特征为站立时头晕，可能会恶化为晕厥、心悸以及踝部蓝紫色变色，同时伴有收缩压显著下降、舒张压升高和心动过速，平卧时上述症状均会消失。我们确定了三个家族，该疾病在这些家族中作为一种外显率降低的常染色体显性性状遗传。对两个最大的家族进行了全基因组扫描，确定了三个多点对数优势（LOD）得分>1.5的区域。在所有三个家族中使用额外的标记对这些区域进行追踪，在18号染色体长臂上产生了显著的连锁证据。在D18S1367位点观察到三个家族的最大多点LOD得分为3.21，尽管最小的家族在整个区域的LOD得分为阴性。在18号染色体长臂存在异质性的情况下有显著的连锁证据，在两个连锁家族中D18S1367位点的最大LOD得分为3.92。确定这些家族中导致直立性低血压障碍的基因，可能会促进对从低血压到高血压这一连续过程中涉及的一般调节途径的理解。
