Liddle综合征患者的临床及基因突变特征

发布时间：2018-06-18 08:15

  本文选题：Liddle综合征 + 临床特征　； 参考：《北京协和医学院》2017年硕士论文

【摘要】：目的:Liddle综合征是一种罕见的常染色体显性遗传性疾病,由编码肾脏远曲小管及集合管的上皮钠通道(ENaC)的基因突变而引起患者出现高血压和低钾血症。目前世界范围报道该病的家系不足百个,且多以单个家系报道为主。本研究拟分析12例Liddle综合征患者的临床及基因特征。方法:回顾性分析了 12例患者的临床资料。抽取患者及部分家系成员外周血,提取基因组DNA,用PCR法扩增ENaC基因β及γ亚单位第13外显子并测序。结果:1、临床特点:12例患者(9例男性,3例女性)均表现为青少年发病的中重度的高血压,起病年龄16±3岁,病程中的最高血压196±22/121±16mmHg。就诊时尽管患者使用1-3种降压药物,但绝大部分患者的血压未控制在理想范围,平均血压为147±12/97±1lmmHg。所有患者均存在低钾血症,病程中最低血钾水平为2.3±0.5 mmol/L。所有患者的立位肾素活性均受抑制,大部分患者立位醛固酮水平也受抑制。5例患者用大剂量安体舒通治疗,治疗后血压均无明显下降。所有患者均用氨苯蝶啶治疗,治疗后患者血压均明显下降,血钾恢复正常。2例患者用氨苯蝶啶治疗后出现血清肌酐水平升高。2、基因分析:对11例患者及部分家系成员进行了基因检测,发现8个基因突变位点,分别为 c.1690CT(p.Arg564Ter)、c.1696CT(p.Arg566Ter)、c.1702CT(p.Gln568Ter)、c.1849CT(p.Pro617Ser)、c.1853CT(p.Pro618Leu)、c.l 806_1807insG(p.Pro603Alafs*5)、c.1848_1849insT(p.Pro617Serfs*5)及c.1854__1855insC(p.Asn619Glnfs*3)。其中,p.Gln568Ter、p.Pro603Alafs 及p.Pro617Serfs突变是新发的突变位点。结论:Liddle综合征患者在临床上表现为早发高血压和低钾血症,合并低肾素活性和低/正常醛固酮水平,用醛固酮受体拮抗剂治疗无效,而上皮钠通道阻滞剂是其有效的治疗药物,但治疗过程中需要严密监测肾功能。本研究在12例Liddle综合征患者中共发现8个基因突变位点,其中3个为新发突变位点。
[Abstract]:Objective to investigate the presence of hypertension and hypokalemia in patients with 1% Liddle syndrome, a rare autosomal dominant disorder caused by mutations in the gene encoding the epithelial sodium channel (ENAC) in the distal convoluted tubules and collecting ducts of the kidney. At present, there are less than 100 families reporting the disease worldwide, most of which are reported by single family. The clinical and genetic characteristics of 12 patients with Liddle syndrome were analyzed. Methods: the clinical data of 12 patients were analyzed retrospectively. Genomic DNA was extracted from peripheral blood of patients and some family members. Exon 13 of ENAC gene 尾 and 纬 subunit was amplified by PCR and sequenced. Results the clinical features of 12 cases of male and 3 female were as follows: the onset age of the disease was 16 卤3 years old, and the course of the disease was 196 卤22 / 121 卤16mm Hg. Although 1-3 antihypertensive drugs were used, the blood pressure of most of the patients was not controlled in the ideal range. The average blood pressure was 147 卤12 / 97 卤1lmmHg. All patients had hypokalemia and the lowest serum potassium level was 2.3 卤0.5 mmol / L in the course of the disease. Renin activity was inhibited in all patients, and aldosterone level was inhibited in most of the patients. 5 patients were treated with high dose of acetonolactone, but blood pressure did not decrease significantly after treatment. All patients were treated with ambendridine and their blood pressure decreased significantly after treatment. 琛，

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