Jackson S N, Williams B, Houtman P, Trembath R C
Department of Genetics, University of Leicester, UK.
J Med Genet. 1998 Jun;35(6):510-2. doi: 10.1136/jmg.35.6.510.
Hypertension is a common multifactorial disorder associated with considerable morbidity and mortality. The kidney plays a major role in the long term regulation of blood pressure. Liddle syndrome (pseudo-hyperaldosteronism) is one of a number of monogenic disorders of salt and water transport. In a kindred with at least four affected members suffering from Liddle syndrome, we confirmed by direct DNA sequencing the identity of a novel heterozygous mutation in h betaENaC, the gene encoding the beta subunit of the amiloride sensitive epithelial sodium channel which is expressed in the distal nephron. Single stranded conformational polymorphism analysis showed cosegregation of the mutant allele within the kindred with the Liddle phenotype. An insertion of an additional cytosine into a string of six located between codons 593 and 595 results in a sequence frameshift and is predicted to produce a protein truncated by 34 amino acids. The availability of a molecular diagnostic tool has implications for the management of hypertension and genetic counselling in families with Liddle syndrome.
高血压是一种常见的多因素疾病，与相当高的发病率和死亡率相关。肾脏在血压的长期调节中起主要作用。利德尔综合征（假性醛固酮增多症）是多种盐和水转运单基因疾病之一。在一个至少有四名成员患有利德尔综合征的家族中，我们通过直接DNA测序确认了hβENaC基因中一个新的杂合突变，该基因编码在远端肾单位表达的氨氯地平敏感上皮钠通道的β亚基。单链构象多态性分析表明，该突变等位基因在家族中与利德尔表型共分离。在密码子593和595之间的六个连续碱基中额外插入一个胞嘧啶会导致序列移码，并预计产生一个截短34个氨基酸的蛋白质。分子诊断工具的可用性对利德尔综合征家族的高血压管理和遗传咨询具有重要意义。
