遗传性肾病研究的现状及未来

　　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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