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

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.

Oral disintegrating desmopressin tablet is effective for partial congenital nephrogenic diabetes insipidus with <i>AVPR2</i> mutation: a case report

“…Oral disintegrating DDAVP was effective in the present case of partial congenital NDI, which was due to an AVPR2 gene mutation, and reduced urine output and water intake by approximately 30%. Previous studies reported a similar efficacy for nasal and oral DDAVP, which decreased urine output by 30-50% (4,6,8). Six AVPR2 mutations, p.A37P, pD85N, p.V88N, p.R104C, p.Y128S, and p.T164C, are associated with the response to high-dose DDAVP (4,7,8,10).…”

“…Previous studies reported a similar efficacy for nasal and oral DDAVP, which decreased urine output by 30-50% (4,6,8). Six AVPR2 mutations, p.A37P, pD85N, p.V88N, p.R104C, p.Y128S, and p.T164C, are associated with the response to high-dose DDAVP (4,7,8,10). High-dose DDAVP was also reportedly effective in patients with partial congenital NDI with AQP2 gene mutations (10,14).…”

“…Although partial congenital NDI is difficult to define, most researchers agree that it is characterized by residual urine concentrating ability (4). According to one definition, the partial type presents with further increases in urine osmolality after vasopressin injection at the plateau phase of water restriction (5).…”

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

“…Males with AVPR2 mutations are symptomatic, whereas heterozygous females are usually asymptomatic [Celebi Tayfur et al, 2018]. However, some heterozygous female carriers have been reported to have NDI; this may be due to random inactivation of the X chromosome [Zhang et al, 2019]. By binding AVPR2, AVP can activate Gs/adenylate cyclase and then regulate the water channel AQP2 in renal tubules and collecting ducts, and finally the concentration of urine [Caletti et al, 2014].…”