發(fā)布時間：2018-06-18 08:15

  本文選題：Liddle綜合征 + 臨床特征��； 參考：《北京協(xié)和醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:Liddle綜合征是一種罕見的常染色體顯性遺傳性疾病,由編碼腎臟遠(yuǎn)曲小管及集合管的上皮鈉通道(ENaC)的基因突變而引起患者出現(xiàn)高血壓和低鉀血癥。目前世界范圍報道該病的家系不足百個,且多以單個家系報道為主。本研究擬分析12例Liddle綜合征患者的臨床及基因特征。方法:回顧性分析了 12例患者的臨床資料。抽取患者及部分家系成員外周血,提取基因組DNA,用PCR法擴增ENaC基因β及γ亞單位第13外顯子并測序。結(jié)果:1、臨床特點:12例患者(9例男性,3例女性)均表現(xiàn)為青少年發(fā)病的中重度的高血壓,起病年齡16±3歲,病程中的最高血壓196±22/121±16mmHg。就診時盡管患者使用1-3種降壓藥物,但絕大部分患者的血壓未控制在理想范圍,平均血壓為147±12/97±1lmmHg。所有患者均存在低鉀血癥,病程中最低血鉀水平為2.3±0.5 mmol/L。所有患者的立位腎素活性均受抑制,大部分患者立位醛固酮水平也受抑制。5例患者用大劑量安體舒通治療,治療后血壓均無明顯下降。所有患者均用氨苯蝶啶治療,治療后患者血壓均明顯下降,血鉀恢復(fù)正常。2例患者用氨苯蝶啶治療后出現(xiàn)血清肌酐水平升高。2、基因分析:對11例患者及部分家系成員進行了基因檢測,發(fā)現(xiàn)8個基因突變位點,分別為 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突變是新發(fā)的突變位點。結(jié)論:Liddle綜合征患者在臨床上表現(xiàn)為早發(fā)高血壓和低鉀血癥,合并低腎素活性和低/正常醛固酮水平,用醛固酮受體拮抗劑治療無效,而上皮鈉通道阻滯劑是其有效的治療藥物,但治療過程中需要嚴(yán)密監(jiān)測腎功能。本研究在12例Liddle綜合征患者中共發(fā)現(xiàn)8個基因突變位點,其中3個為新發(fā)突變位點。
[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 緯 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 鹵3 years old, and the course of the disease was 196 鹵22 / 121 鹵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 鹵12 / 97 鹵1lmmHg. All patients had hypokalemia and the lowest serum potassium level was 2.3 鹵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，

本文編號：2034799