四例脂蛋白肾病患者载脂蛋白E基因突变筛查

Screening for apolipoprotein E gene mutations in 4 patients with lipoprotein glomerulopathy

目的通过对4例脂蛋白肾病患者及家系成员载脂蛋白E(apoE)基因的分析,研究脂蛋白肾病的发病机制。方法调查患者家系情况,对其中2例患者的家系成员进行尿常规筛查及血肌酐、血脂和血清脂蛋白的检测。PCR法扩增4例患者apoE基因的外显子,DNA测序,发现突变后,寻找限制性内切酶酶切位点。使用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)的方法筛查正常对照及其家系成员。结果4例脂蛋白肾病患者中有2例携带杂合的apoE基因缺失突变(142-144—0),2例患者携带杂合的apoE点突变(Arg25Cys),2种突变均可见于尿液检查正常的亲属,并均表现为apoE升高。结论4例脂蛋白肾病的患者中发现两种apoE基因的突变,apoE Arg25Cys和apoE(142-144-0)。结合既往的研究结果,apoE(142- 144-0)同时见于5例(本研究2例,前期研究3例)患者,为中国脂蛋白肾病患者常见的致病性基因突变。患者家系成员中的携带者可以不表现出肾脏病。

Objective To study the mutations of apolipoprotein E （apoE）gene in 4 Chinese hpoprotein glomerulopathy（LPG）patients and their family members, and to investigate the pathogenesis of LPG. Methods Urinalysis was performed on the family members of two patients, and they were screened for the level of serum creatinine, serum lipid and serum lipoprotein. The mutation of apoE gene was detected by direct sequencing after PCR of apoE exons. PCR RFLP was used to identify the mutations in family members. Results Two kinds of mutation of apoE gene were identified in these 4 patients. A 9 bp deletion in exon 4, resulting in a 3-amino acid deletion （residues 142-144- 0） was confirmed in 2 patients and a point mutation in exon 3 resulting in Arg25Cys was found in another 2 patients. Above mutations were found in the patients＇ relatives who had normal urinalysis results. Conclusions The 3-amino acid deletion （142-144-0） of apoE gene is the common mutation to cause LPG in Chinese patients. Both mutations could be found in their relatives without LPG.