一个先天性肾性尿崩症合并高尿酸血症的家系研究  

A family study of congenital nephrogenic diabetes insipidus combined with hyperuricemia

作　　者：赵琳琳[1] 夏雪 潘梦醒 赵艳艳[1] Zhao Linlin;Xia Xue;Pan Mengxing;Zhao Yanyan(Department of Endocrinology and Metabolism,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Endocrinology,Puyang People′s Hospital,Puyang 457000,China)

机构地区：[1]郑州大学第一附属医院内分泌与代谢病科,450052 [2]濮阳市人民医院内分泌科,457000

出　　处：《中华内分泌代谢杂志》2023年第4期320-326,共7页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的探讨先天性肾性尿崩症(congenital nephrogenic diabetes insipidus,CNDI)合并高尿酸血症的临床及遗传学特点、可能机制及治疗策略。方法收集并分析1例CNDI合并高尿酸血症的患儿及家系成员的临床表现及实验室检查特点,采用全外显子测序法检测先证者全部基因各个外显子的序列变异情况,采用PCR-Sanger测序法验证该家系其他成员的AVPR2与ABCG2基因的序列变异。收集2015年1月至2022年1月期间郑州大学第一附属医院首次确诊CNDI的年龄≤14岁的患者,统计其血尿酸水平。结果临床诊断CNDI仅先证者1人,其余家系成员均无多饮、多尿表现。高尿酸血症除先证者外,还包括先证者父亲。全外显子测序显示先证者存在AVPR2基因变异(p.S331R)与ABCG2基因变异(p.N308K),前者为半合子,X连锁隐性遗传,来源于母亲,母亲为杂合变异;后者为杂合变异,常染色体显性遗传,来源于父亲。该家系中高尿酸血症患者的尿酸排泄分数(FEUA)先证者为3.1%,父亲为2.7%。回顾12例年龄≤14岁确诊CNDI患者的临床资料:男性11例,女性1例,就诊年龄3个月~14岁,合并高尿酸血症者5例。结论儿童CNDI患者可能合并高尿酸血症,氢氯噻嗪联合苯溴马隆方案效果良好。该家系中的AVPR2基因变异(p.S331R)和ABCG2基因变异(p.N308K)的致病性需进一步深入研究。Objective To investigate the clinical and genetic characteristics,pathogenesis and treatment strategy of congenital nephrogenic diabetes insipidus(CNDI)combined with hyperuricemia.Methods The clinical manifestations and laboratory data of an infant patient diagnosed as CNDI with hyperuricemia and his family members were collected and retrospectively analyzed.Whole exome sequencing(WES)was applied to detect the proband′s genome variation of each exon and suspected variants of AVPR2 and ABCG2 were verified by PCR-Sanger sequencing of members from his pedigree.Furthermore,we retrospectively collected the serum uric acid levels of patients(≤14-year-old)with CNDI in the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2022.Results The proband was clinically diagnosed with CNDI and the rest of the family members had no symptoms of polydipsia or polyuria.In addition to the proband,his father was also suffered from hyperuricemia.WES showed that the proband carried a hemizygous AVPR2 gene variation(p.S331R)and a heterozygous ABCG2 gene variation(p.N308K).The former was X-linked recessive inheritance from his mother,and the latter was autosomal dominant inheritance from the father.Fraction excretion of uric acid(FEUA)of the proband and his father with hyperuricemia were 3.1%and 2.7%,respectively.Twelve children(≤14-year-old)were diagnosed with CNDI from the respective study.Among all the cases,11 patients were male and 1 was female,ranging from 3-month to 14-year-old.Five patients were accompanied with hyperuricemia.Conclusion Children with CNDI may be complicated with hyperuricemia,and the regimen of hydrochlorothiazide combined with benzbromarone is effective.The pathogenicity of the AVPR2 gene variation(p.S331R)and ABCG2 gene variation(p.N308K)in this pedigree needs to be further studied.

关 键 词：先天性肾性尿崩症 儿童高尿酸血症 AVPR2基因变异 ABCG2基因变异 治疗 

分 类 号：R725.8[医药卫生—儿科]