精氨酸加压素2型受体基因突变所致遗传性尿崩症临床特点分析

Clinical characteristics of diabetes insipidus caused by mutations of arginine vasopressin receptor type 2 gene:an analysis of 22 cases

目的通过对22例确诊精氨酸加压素2型(AVPR2)基因突变的遗传性肾性尿崩症患者的临床特点进行总结,分析基因型与临床表型之间的相关性。方法收集22个家系及其成员病史及外周血标本,通过生化检查、磁共振影像和AVPR2基因的聚合酶链式反应,确诊为X-连锁隐性遗传性肾性尿崩症。结果 22例先证者均为男性,其确诊年龄为(15.6±1.9)岁,病程(14.5±1.9)年,尿量为(10 L/24 h),61.9%的患者出现泌尿系并发症。共筛查到18个突变位点共5种突变类型,其中包括5个国际上尚未报道的新发突变位点:c.752_780delCGCCGGACAGGCAGCCCCGGTGAGGGAGC(R251PfsX96),c.349 T>G(Y117D),c.500 C>G(S167W),c.938T>G(L313R),c.1007 T>C(L336P)。结论 X-连锁隐性遗传性肾性尿崩症患者多早期发病,烦渴、多饮、多尿及低比重尿为其主要临床表现,半数患者出现病程相关的泌尿系并发症,大部分患者对间断的噻嗪类利尿剂+阿米洛利联合使用疗效较好。基因检测手段对该病的诊断提供了有利依据,并可进一步指导优生优育。

Objective To investigate the clinical and biochemical features of nephrogenic diabetes insipidus （NDI） in patients with mutations of arginine vasopressin receptor type 2 gene （AVPR2）, and to find the correlation between the genotypes and clinical phenotypes. Methods Medical histories and peripheral blood samples of 22 NDI probauds and their family members were collected and final diagnoses of X-linked NDI were made by biochemical tests, magnetic resonance imaging （MRI） and polymerase chain reaction （PCR） of AVPR2 gene. Results All of the 22 probands were males with a mean diagnosed age of （15.6 ± 1.9）years. The average urine output was 10 L/24 h, and 61.9% patients reported urinary complications. Sequencing revealed 18 AVPR2 gene mutations, including 5 novel mutations, which were c. 752_ 780delCGCCGGACAGGCAGCCCCGGTGAGGGAGC （ R251PfsX96 ）, c. 349T 〉 G （ Y117D ）, c. 500C 〉 G （ S167W ）, c. 938 T 〉 G（L313R） , and c. 1007 T 〉 C（L336P）. Conclusion The onset ages of NDI patients are early ,with the main clinical manifestations such as thirst, polydipsia, polyuria and low specific gravity of urine. Almost half patients have the pathogenesis-related urinary complications. Intermittent thiazide and amiloride treatments have good effect in most patients. Genetic detection provides a favorable evidence for diagnosis of NDI, and can further guide prenatal and postnatal care.