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

目的 探讨中国人的常染色体显笥遗传垂体性尿崩症（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）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2增加了两亿异常条带，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扩培产物在使用不同的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1826－1831位置两个连续的GAG中脱薄一个GAG.珲种突变导致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。

Mutation of autosomal dominant neurohypophyseal diabetes insipidus in a Chinese pedigree

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.