A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus: A case report

Abstract

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.

Figure 1

Pedigree of X-linked nephrogenic diabetes insipidus in the patient's family.

Figure 2

DNA sequencing results for the 75-year-old female with suspected diabetes insipidus and her 3 first-degree relatives (her brother, sister and son), two second-degree relatives (her niece and nephew) and one third-degree relative (her grandnephew, that is her niece's son). Arrows represent the mutation site. (A) DNA sequencing revealed a novel missense mutation [c. 492G>C (arrow), resulting in a substitution of Trp with Cys at codon 164] in the AVPR gene, which was heterozygous in proband, the proband's sister and niece. (B) DNA sequencing revealed a missense mutation which was hemizygous in the proband's son, brother and nephew. (C) DNA sequencing showed normal in the proband's grandnephew.