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目的 探讨中国人的常染色体显性遗传垂体性尿崩症 (ADNDI)的分子发病机制。方法 对一个家系中 4例ADNDI患者、4例未发病者及 1例来自其他家庭的患者的精氨酸加压素 运载蛋白Ⅱ (AVP NPⅡ )基因外显子 1和 2进行聚合酶链反应 单链构像多态性 (PCR SSCP)分析及基因测序研究。结果 SSCP分析表明 :ADNDI的同一个家系中的患者、正常人及来自其他家系非遗传尿崩症患者的AVP NPⅡ外显子 1的泳带之间没有区别 ;但ADNDI家系患者AVP NPⅡ外显子 2增加了两个异常条带 ,为突变杂合子。ADNDI家系中患者 (先证者、先证者祖母 )AVP NPⅡ基因外显子2PCR扩增产物在使用不同的DNA测序仪、采用正反引物测序均显示同样结果 ,即在AVP NPⅡ基因第 182 6 1831位置两个连续的GAG中脱落一个GAG。这种突变导致AVP NPⅡ基因合成的NPⅡ前体缺少Glu47。由于NPⅡ多肽的Glu47同AVP形成一个盐桥 ,缺乏Glu47将使AVP同NPⅡ的粘着力下降 ,加速AVP的分解。结论 碱基缺失为中国人常染色体显性遗传垂体性尿崩症发病原因之一。
Objective To investigate the molecular pathogenesis of Chinese autosomal dominant pituitary diabetes insipidus (ADNDI). Methods Polymerase chain reaction (PCR) was performed on exon 1 and 2 of arginine vasopressin transporter Ⅱ (AVP NPⅡ) gene in four ADNDI patients, four patients without disease and one patient from other families in one pedigree PCR SSCP Analysis and Gene Sequencing. Results SSCP analysis showed that there was no difference between the bands of AVP NPⅡ exon 1 in patients with ADNDI in the same pedigree, normal persons and non-genetic diabetes insipidus patients from other families; however, in patients with ADNDI pedigree, AVP NPⅡ exon 2 added two abnormal bands, as mutant heterozygotes. In the ADNDI pedigree (proband, proband grandmother) AVP NPⅡ gene exon 2PCR amplification products using different DNA sequencer, using forward and reverse primer sequencing showed the same result, that AVP NPⅡ gene 182d6 One GAG was shed at 1831 in two consecutive GAGs. This mutation resulted in the absence of Glu47 in the NPII precursor synthesized by the AVP NPII gene. Since Glu47 of NPⅡ polypeptide forms a salt bridge with AVP, the lack of Glu47 will reduce the adhesion of AVP to NPⅡ and accelerate the decomposition of AVP. Conclusion Base deletion is one of the causes of autosomal dominant pituitary diabetes insipidus in Chinese.