Uehara Y, Sasaguri M, Kinoshita A, Tsuji E, Kiyose H, Taniguchi H, Noda K, Ideishi M, Inoue J, Tomita K, Arakawa K
Department of Internal Medicine, Fukuoka University, School of Medicine, Japan.
J Hypertens. 1998 Aug;16(8):1131-5. doi: 10.1097/00004872-199816080-00008.
Liddle's syndrome is an autosomal inheritable disorder that causes hypertension due to excess function of sodium channel.
To analyze the DNA sequence of the amiloride-sensitive epithelial sodium channel (ENaC) in three patients who had low-renin hypertension with hypokalemia. The patients included a 24-year-old woman and her 20-year-old brother whose mother was hypertensive. The third patient was a 15-year-old girl with no family history of hypertension.
The DNA sequence of the ENaC was analyzed as follows. Venous blood samples were collected from the patients and total genomic DNA was prepared by standard methods. Specific primers were used for direct polymerase chain reaction; one set of primers for amplifying the C terminus (codon 523-638) of the , subunit of ENaC, and two sets of primers for amplifying the C terminus (codons 525-587 and 568-650) of the y subunit of ENaC. Polymerase chain reaction products were purified and subjected to direct DNA sequence analysis.
Direct sequence analysis demonstrated the presence of a single-base substitution in one segment of the 0 subunit of ENaC, a C-T transition that changed the encoded Pro (CCC) at codon 616 to Ser (TCC) in the siblings (cases 1 and 2). In case 3, we found a missense mutation of Pro (CCC) to Leu (CTC) at codon 616. Case 3 is considered to be sporadic, since DNA sequencing of the PY motif of her parents gave normal results.
The DNA sequences of the ENaC in three patients with Liddle's syndrome were analyzed. In one family case, we found a new missense mutation of Pro (CCC) to Ser (TCC) at codon 616 in the 0 subunit of ENaC. A genetic analysis of the amiloride-sensitive epithelial sodium channel is recommended in assessing patients with low-renin, salt-sensitive hypertension whose blood pressure is not responsive to spironolactone treatment.
利德尔综合征是一种常染色体显性遗传病，因钠通道功能亢进导致高血压。
分析3例低肾素性高血压伴低钾血症患者的氨氯地平敏感型上皮钠通道（ENaC）的DNA序列。患者包括一名24岁女性及其20岁的弟弟，他们的母亲患有高血压。第三位患者是一名15岁女孩，无高血压家族史。
按如下方法分析ENaC的DNA序列。采集患者静脉血样本，采用标准方法制备总基因组DNA。使用特异性引物进行直接聚合酶链反应；一组引物用于扩增ENaC的β亚基的C末端（密码子523 - 638），两组引物用于扩增ENaC的γ亚基的C末端（密码子525 - 587和568 - 650）。聚合酶链反应产物经纯化后进行直接DNA序列分析。
直接序列分析显示，在ENaC的β亚基的一个片段中存在单碱基替换，即C - T转换，该转换使同胞（病例1和2）中密码子616处编码的脯氨酸（CCC）变为丝氨酸（TCC）。在病例3中，我们在密码子616处发现了脯氨酸（CCC）到亮氨酸（CTC）的错义突变。病例3被认为是散发性的，因为对其父母的PY基序进行DNA测序结果正常。
分析了3例利德尔综合征患者的ENaC的DNA序列。在一个家族病例中，我们在ENaC的β亚基的密码子616处发现了脯氨酸（CCC）到丝氨酸（TCC）的新错义突变。对于血压对螺内酯治疗无反应的低肾素、盐敏感性高血压患者，建议对氨氯地平敏感型上皮钠通道进行基因分析。
