一个先天性肾性尿崩症家系AVPR2基因的突变分析

Analysis of AVPR2 gene mutation in a pedigree affected with congenital nephrogenic diabetes insipidus

目的对1例先天性肾性尿崩症患者及其家系进行AVPR2基因突变检测，探讨其分子发病机制。方法收集先证者的临床资料，抽取先证者及5名家系成员的外周血提基因组DNA，应用PCR扩增AVPR2基因的全部编码区并直接测序。结果先证者表现为出生后即开始多尿喜饮，泌尿系统CT提示显著双侧肾积水及输尿管扩张，用醋酸去氨加压素治疗无效，用双氢克尿噻治疗部分有效。DNA测序结果显示先证者AVPR2基因第2外显子存在c．295T〉C（P．W99R）错义突变，先证者母亲及外祖母AVPR2基因第2外显子存在c．295T〉C杂合突变。结论AVPR2基因第2外显子c．295T〉C突变可能是该先天性肾性尿崩症家系患病的原因。

Objective To detect potential mutation in a pedigree affected with congenital nephrogenie diabetes insipidus （NDI）. Methods Clinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 （AVPR2） gene was amplified by PCR and directly sequenced. Results The patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c. 295 T〉C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation. Conclusion The congenital NDI in the patient was probably due to mutation of the AVPR2 gene.