Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus
Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus
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DOI：
10.1007/s40618-021-01607-3
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发表时间：
2021-06-08
影响因子：
5.4
通讯作者：
Xia, W.
中科院分区：
文献类型：
--
作者：
Li, Q.;Tian, D.;Xia, W.
目的探讨AVPR2基因突变引起的先天性肾源性尿崩症的基因型和表型，AVPR2基因突变在中国人群中罕见且研究有限。方法对北京某科28个NDI家族的88例患者进行AVPR2基因突变筛选。对医疗记录进行回顾性审查和分析。进行基因型和表型分析。结果共鉴定出23个AVPR2突变，其中6个为新突变（p.Y117D、p.W208R、p.L313R、p.S127del、p.V162Sfs*30和p.G251Pfs*96）。发病年龄从1周至3岁不等。常见的表现为烦渴多尿（100%）和间歇性发热（57%）。21%和14%的患者有身材矮小和精神障碍。尿SG和渗透压降低，而血清渗透压和钠升高。泌尿系超声检查结果显示肾积水（52%）、输尿管扩张（48%）、膀胱壁增厚或残余尿增多（32%），导致间歇性导尿（7%）、膀胱造瘘（11%）和双肾造瘘（4%）。老年患者出现泌尿系统缺陷。基因型和表型分析显示，非错义突变患者的血清钠水平高于错义突变患者。在中国人群中由AVPR2突变引起的第一个也是最大的NDI病例系列中，我们建立了遗传谱并描述了临床数据，报告了6个新的突变。此外，我们发现基因型与表型相关。这一发现拓宽了罕见的由AVPR2突变引起的先天性NDI的基因型和表型谱，为研究AVPR2的分子生物学提供了依据。
Aims To investigate genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2 mutations, which is rare and limitedly studied in Chinese population. Methods 88 subjects from 28 families with NDI in a department (Beijing, PUMCH) were screened for AVPR2 mutations. Medical records were retrospectively reviewed and characterized. Genotype and phenotype analysis was performed. Results 23 AVPR2 mutations were identified, including six novel mutations (p.Y117D, p.W208R, p.L313R, p.S127del, p.V162Sfs*30 and p.G251Pfs*96). The onset-age ranged from 1 week to 3 years. Common presentations were polydipsia and polyuria (100%) and intermittent fever (57%). 21% and 14% of patients had short stature and mental impairment. Urine SG and osmolality were decreased, while serum osmolality and sodium were high. Urological ultrasonography results showed hydronephrosis of the kidney (52%), dilation of the ureter (48%), and thickened bladder wall or increased residual urine (32%), led to intermittent urethral catheterization (7%), cystostomy (11%) and binary nephrostomy (4%). Urological defects were developed in older patients. Genotype and phenotype analysis revealed patients with non-missense mutations had higher levels of serum sodium than missense mutations. Conclusion In the first and largest case series of NDI caused by AVPR2 mutations in Chinese population, we established genetic profile and characterized clinical data, reporting six novel mutations. Further, we found genotype was associated with phenotype. This knowledge broadens genotype and phenotype spectrum of rare congenital NDI caused by AVPR2 mutations, and provides basis for studying molecular biology of AVPR2.