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遗传性肾病研究的现状及未来

来源:论文汇编 作者:自动采集 2005-1-1
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摘要: 遗传性肾病(inheritedkidneydiseases)是由基因突变所致,并按孟德尔定律遗传子代的一组肾脏疾病,包括遗传性肾囊肿疾病,如常染色体显性遗传型多囊肾病(autosomaldominantpolycystickidneydisease,ADPKD)。遗传性肾小球疾病,如遗传性肾炎(Alportsyndrome,AS)、薄基底膜肾病(thinbasementmembranedisease,TBMD)和Fabr......



  遗传性肾病(inheritedkidneydiseases)是由基因突变所致,并按孟德尔定律遗传子代的一组肾脏疾病,包括遗传性肾囊肿疾病,如常染色体显性遗传型多囊肾病(autosomaldominantpolycystickidneydisease,ADPKD);遗传性肾小球疾病,如遗传性肾炎(Alportsyndrome,AS)、薄基底膜肾病(thinbasementmembranedisease,TBMD)和Fabry病;遗传性肾小管疾病,如家族性抗维生素D佝偻病(familialvitamineDresistantrickets,VDRR);以及遗传代谢性肾病,如胱氨酸肾病等。过去,对遗传性肾病认识不足,发现率低。随着现代分子生物学技术的进步,遗传性肾病的基因突变检测,发病机制研究及诊断技术水平有了很大提高,基因治疗也给遗传性肾病患者带来了治愈的希望。ADPKD是一种最常见的单基因遗传性肾病,人群发病率约1/1000t[1]。家系中代代有人患病,子代患病机率为50%,男女患病相等,患者等位基因为杂合子是其遗传特点。目前ADPKD研究主要有以下进展:(1)分子遗传学研究:研究表明引起ADPKD的突变基因至少有3种,按发现先后,分别称为PKD1、PKD2和PKD3。PKD3尚未在染色体上定位,PKD1和PKD2引起ADPKD分别占85%和15%,均已在染色体上定位和克隆。PKD1位于第16人染色体短臂1区3带上(16p13),蛋白质产物是由4302个氨基酸残基构成的一种糖蛋白,称为多囊蛋白-1,位于细胞膜上[2]。本刊今期发表的文章表明多囊蛋白-1在正常肾小球囊和肾小管上皮细胞均有表达,在胎肾肾小管和多囊肾衬里上皮表达显著增强。PKD2位于第4人染色体长臂2区1带至3带之间(4q21~23),翻译产物称为多囊蛋白-2。由968个氨基酸残基构成,同样是一种膜蛋白。多囊蛋白功能未明,推测它们主要介导细胞-细胞,细胞-基质A之间的相互作用,促进上皮细胞分化,维持膜蛋白正(全文见PDF)参考文献:

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