A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus A case report
A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus A case report
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亚洲遗传性肾性尿崩症家族中的一个新的 AVPR2 错义突变一例报告
DOI：
10.1097/md.0000000000015348
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发表时间：
2019-04-01
期刊：
影响因子：
1.6
通讯作者：
Tian, Dean
中科院分区：
文献类型：
--
作者：
Zhang, Min;Yu, Qin;Tian, Dean
基本原理：X连锁肾源性尿崩症（NDI）是一种罕见的遗传性疾病，其特征是肾脏对精氨酸加压素（AVP）的抵抗。其诊断在临床上具有挑战性。分子遗传学分析的应用可以提供一个快速和明确的diagnosis.Patient concerns：一个75岁的女人提出与复发性恶心和呕吐被收进消化科。该患者有明显的多饮和多尿家族史。抗利尿激素精氨酸加压素受体2（AVPR 2）的测序分析显示，在外显子2的新的错义突变p.Trp164Cys（c.492G>G/C）。在患者的姐姐和侄女中存在杂合突变，而在她的儿子，兄弟和父母中存在突变。该位点位于X染色体Xq 28上，其突变可导致X连锁隐性NDI。AVPR 2基因的p.Trp164Cys突变未见文献报道。通过几种预测方法，包括SIFT和PolyPhen-2，预测该突变可能是有害的。该基因其他检测区域无明显异常变异。诊断：根据患者家族史及DNA测序分析，诊断为X连锁NDI干预及转归：经去氨加压素、止吐药及大量输注葡萄糖治疗后，患者尿量减少，电解质紊乱得到纠正，恶心呕吐症状逐渐消失。教训：对疑似先天性NDI的患者应进行AVPR 2、AVP和AQP 2基因测序分析。明确的诊断可以使患者受益，避免不必要的检查。
Rationale: X-linked nephrogenic diabetes insipidus (NDI) is a rare inherited disease, and is characterized by renal resistance to arginine vasopressin (AVP). Its diagnosis can be clinically challenging. The application of molecular genetic analysis can provide a rapid and definitive diagnosis.Patient concerns: A 75-year-old woman presented with recurrent nausea and vomiting was admitted to the Department of Gastroenterology. The patient had a strong family history of polydipsia and polyuria. Sequencing analysis of the antidiuretic hormone arginine vasopressin receptor 2 (AVPR2) revealed the novel missense mutation p.Trp164Cys (c.492G>G/C) in exon 2. There was a heterozygous mutation in the patient's sister and niece, while there was a mutation in her sons, brother and nephews. The locus is located on the X chromosome Xq28, and its mutation can lead to X linked recessive NDI. The p.Trp164Cys mutation of AVPR2 gene has not been reported in literature before. The mutation was predicted to be probably damaging by several prediction methods, including SIFT and PolyPhen-2. There was no significant abnormal variation in other detection regions of the gene. And there was also no abnormal variation in AVP and AQP2 genes in this family.Diagnosis: X-linked NDI was diagnosed according to the patient's family history and DNA sequencing analysis.Interventions and outcomes: After treated with desmopressin, antiemetic drugs and massive infusion glucose transfusion, the patient's urine volume decreased and electrolyte disturbance was corrected, and the symptoms of nausea and vomiting gradually disappeared.Lessons: The patients with suspected congenital NDI should undergo genetic sequencing analysis of AVPR2, AVP and AQP2 genes. A definitive diagnosis can benefit patient and avoid unnecessary investigations.