一中国人家系常染色体显性遗传垂体性尿崩症基因突变研究  

Mutation of autosomal dominant neurohypophyseal diabetes insipidus in a Chinese pedigree

作　　者：陈育才[1] 谢文煌[1] 王柠[2] 慕容慎行[2] 黄妙辉[1] 黄梅芳[1] 

机构地区：[1]福建医科大学附属第一医院儿科,福州350005 [2]福建医科大学附属第一医院神经科,福州350005

出　　处：《中华内分泌代谢杂志》2001年第1期24-26,共3页Chinese Journal of Endocrinology and Metabolism

摘　　要：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 elucidate the molecular mechanism of autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) in Chinese. Methods A Chinese family with ADNDI was studied. Polymerase chain reaction single strand conformation polymorphisms (PCR SSCP) of exon 1 and exon 2 of arginine vasopressin neurophysin Ⅱ (AVP NPII) gene were performed in 4 patients and 4 normal phenotypic members of the pedigree and 1 patient from other family. Direct DNA sequencing of PCR amplified geomic DNA in exon 2 are carried out. Results In exon 1, the affected patients and unaffected people in same kindred and a nonfamilial insipidus from other family had the same strand in SSCP analysis. But there were differences in SSCP analysis from exon 2 as follows: besides having the same strand as healthy man in same kindred or a nonfamilial affected patient, SSCP analysis showed that affected patients from ADNDI had two new different strands. The results were confirmed by direct DNA sequencing of PCR amplified geomic DNA. A 3 base pair deletion (GAG) out of two consecutive GAG sequence (nucleotides 1826 1831) was identified in affected individual with ADNDI. This mutation should yield an abnormal AVP precursor lacking Glu47 in its neurophysin Ⅱ moeity. Since Glu47 is essential for NP molecules to form a salt bridge with AVP, the function of NP as a carrier proetin for AVP would be impaired which leads to acceleration proteolytic degradation. Conclusion The nucleotides deletion in the coding region for neurophysin Ⅱ gene appears to be one of the causes of autosomal dominant neurohypophyseal diabetes insipidus in Chinese.

关 键 词：尿崩症 遗传学 基因突变 染色体显性遗传垂体性 ADNDI 

分 类 号：R584.3[医药卫生—内分泌]