20例Gitelman综合征中高发突变的基因型与表型关系

发布时间：2018-04-29 17:55

  本文选题：Gitelman综合征 + 突变　； 参考：《青岛大学》2017年硕士论文

【摘要】：目的:对收集的青岛地区和枣庄地区的20例确诊的Gitelman综合征患者进行相关的致病基因SLC12A3的突变基因型及表型进行分析比较,旨在探讨其中高发突变的基因型与表型的关系。方法:本研究组选取2013至2016年在青岛大学附属医院和枣庄矿业集团中心医院住院治疗的20例经基因测序确诊的Gitelman综合征患者。其中男性患者13例,女性患者7例,平均年龄(33± 12)岁。收集20例患者的一般临床资料和相关的实验室检查结果:性别、发病年龄、症状、体征、血压、血钾、血镁、血碳酸氢根、血浆肾素、血浆醛固酮、24h尿钙/尿肌酐。查找20例经基因确诊患者的突变基因型。将不同突变基因型的患者的一般临床资料和实验室检查结果进行相应的分析比较。对50例非相关的健康患者进行相关的基因测序,查找有无SLC12A3基因上的突变。采用SPPSS13.0软件进行统计学处理。结果:20例确诊的患者中14例患者表现为四肢乏力,4例患者表现为手足搐搦,1例患者表现为多尿、夜尿增多,6例患者无相应的临床症状,仅仅在查体中发现了低血钾,5例患者发病年龄"f 18岁。20例患者均有低钾血症,16例患者有低镁血症,20例患者血碳酸氢根均大于27mmol/L,20例患者均有低尿钙(24 h尿Ca2+/Cr0.1摩尔比)。20例患者中都发现SLC12A3基因上的突变,其中共发现了 15个相关的突变位点,其中错义突变 9 个(Cys430Gly、Leu571Pro、Thr60Met、Asp486Asn、Glu429Lys、Ala264Gly、Ser283Thr、Thr163Met、Arg913Gln),缺失突变 5 个(1384delG、346-353delACTGATGG、2883-2884delAG、1740delC、2877-2878delAG),1 个插入突变(997insCys),其中杂合突变2例,纯合突变1例,复合杂合突变17例,有8例患者发现了 Ala264Gly的突变,发生率约为21.1%(8/38)。有2例患者仅存在1个位点突变(2/20=10%),远远低于既往文献报道的40%。50例非相关的健康患者中未检测出SLC12A3基因上的突变。ALa264GLy携带者的发病年龄、四肢乏力、手足搐搦、多尿(夜尿增多)等症状的发生与携带其他突变的患者无显著的统计学差异,实验室检查方面ALa264GLy携带者的血钾、血镁、血碳酸氢根、血浆血管紧张素、血浆醛固酮、24h尿钙/尿肌酐与携带其他突变的患者亦无显著的统计学差异。结论:不同地区Gitelman综合征患者的表型及相关的突变基因可能有所不同。Gitelman综合征表型的多样性和异质性是基因型和表型的联系较难以确定的关键因素,而Gitelman综合征患者表型的呈现是多个致病突变基因相互共同作用的结果;后天的饮食、性别以及环境的影响也是不能忽略的因素。目前尚无直接的证据支持本研究中的高发突变ALa264GLy与表型有明确的关系。
[Abstract]:Objective: to analyze and compare the genotypes and phenotypes of the related pathogenic gene SLC12A3 in 20 patients with Gitelman syndrome in Qingdao and Zaozhuang, in order to explore the relationship between the genotype and phenotype of the high incidence mutation. Methods: 20 patients with Gitelman syndrome diagnosed by gene sequencing were selected from 2013 to 2016 in Qingdao University affiliated Hospital and Zaozhuang Mining Group Central Hospital. There were 13 males and 7 females with an average age of 33 卤12 years. The general clinical data and related laboratory findings of 20 patients were collected: sex, age of onset, symptoms, signs, blood pressure, blood potassium, blood magnesium, blood bicarbonate, plasma renin, plasma aldosterone 24 hours urine calcium / urinary creatinine. The mutation genotypes of 20 patients confirmed by gene were found. The general clinical data and laboratory results of patients with different genotypes were analyzed and compared. A total of 50 unrelated healthy patients were sequenced to identify mutations in the SLC12A3 gene. SPPSS13.0 software was used for statistical processing. Results of the 20 confirmed cases, 14 cases were characterized by fatigue, 4 cases showed tetany, 1 case showed polyuria, 6 cases with nocturia had no corresponding clinical symptoms. The age of hypokalemia was found only in 5 patients with hypokalemia. "f 18 years old. 20 cases all had hypokalemia. 16 cases had hypomagnesemia. 20 cases had blood bicarbonate > 27 mmol 路L ~ (-1). All 20 cases had hypocalcemia for 24 h and urine Ca2 / Cr _ (0.1) mole." A mutation in the SLC12A3 gene was found in 20 patients. 鍏朵腑鍏卞彂鐜颁簡 15涓�鐩稿叧鐨勭獊鍙樹綅鐐�,鍏朵腑閿欎箟绐佸彉 9 涓，

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