Mutation Analysis of AVPR2 and AQP2 Gene in Chinese Patients with Congenital Nephrogenic Diabetes Insipidus

To detect mutations of the aquaporin 2 gene（AQP2） and the arginine vasopressin V2 receptor gene（AVPR2） of Chinese congenital nephrogenic diabetes insipidus, and to establish the foundation for further studying the emergence mechanism of the disease and clinical diagnosis, all the exons and part of introns of AQP2 and AVPR2 genes were amplified with intronic primers, using genomic DNA extracted from three patients with congenital nephrogenic diabetes insipidus and two mothers as template, PCR product was ligated into a T-vector and then sequenced. The result was compared with the database sequence to identify the mutable sites via a BLAST search, the incidence of every mutation was analyzed, and the putative transcription factor binding sites that maybe disturbed were analyzed by MAPPER. Mutation g.1394A〉G in exon 3 of AVPR2 was detected in all the subjects, g.861C〉T（S167L） in exon 2 of AVPR2 and IVS1＋3G〉A in intron of AQP2 were detected, respectively, in two patients, and c.836A〉C in 3′ untranslated region of AQP2 was detected in two patients and one mother. Four mutations were identified. g.1394A〉G of AVPR2 and c.836A〉C of AQP2 have high incidence in patients with nephrogenic diabetes insipidus. Detection on the two sites may become auxiliary diagnosis index of congenital nephrogenic diabetes insipidus.

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2(c.541C>T)in a neonate:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renaldisorder that is caused by mutations in AVPR2 or aquaporin 2 (AQP2). Up tonow, there are few reports about CNDI in neonates. Early clinical manifestationsof CNDI in neonates are atypical. A lack of understanding of the disease byclinicians causes frequent misdiagnoses or missed diagnoses, which may result infailure to administer treatments in time and ultimately leads to severecomplications. In this study, clinical data of a case of AVPR2 gene mutationinducedCNDI, which was confirmed by genetic testing, were retrospectivelyanalyzed to improve our understanding of this disease.CASE SUMMARY On February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 dperiod of pyrexia. The patient’s symptoms included recurrent pyrexia,hypernatremia and hyperchloremia, which were difficult to treat. The patient wasfed on demand, and water was additionally provided between milk intakes. Acombination treatment of hydrochlorothiazide and amiloride was administered.After the treatment, body temperature and electrolyte levels returned to normal,the volume of urine was significantly reduced and the patient was subsequentlydischarged. Genetic tests confirmed that the patient carried the AVPR2 genemissense mutation c.541C>T (P.R181C), and the patient’s mother carried aheterozygous mutation at the same locus. After clinical treatment with acombination of hydrochlorothiazide and amiloride, the body temperature andelectrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth anddevelopment were observed.CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecificwith some patients merely showing recurrent fever and electrolyte disturbance.Genetic testing of AVPR2 and AQP2 can be used for screening and geneticdiagnosis of CNDI.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.