A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr108Met Variant of Aquaporin 2

Ma, Lina; Wu, Dengyan; Wang, Xingmin; Yang, Yonghong

doi:10.3389/fped.2020.00015

Cited by 4 publications

(4 citation statements)

References 20 publications

(27 reference statements)

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“…There were few reports studied the endocrine hormones in CNDI patients. One study investigated the treatment of rhGH in a CNDI case cause by AQP2 variation, but the endocrine hormones and the response of rhGH were not well-documented ( 26 ). In present study, the proband's height SDS before rhGH treatment was −4.31 SDS, and he had a low peak GH level as well as low IGF-1 level, suggesting a possible diagnosis of GH deficiency.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family

Guo

et al. 2021

Front. Pediatr.

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Background: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease that is caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 (AQP2). Functional analysis of the mutated receptor is necessary to verify the impact of the mutation on receptor function and suggest some possible therapeutic strategies for specific functional defects.Methods: Family history and clinical information were collected. Whole-exome sequencing and sanger sequencing were performed to determine the potential genetic cause of diabetes insipidus. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. Bioinformatic analysis was performed to predict the function of the identified variation. Moreover, wild-type and mutated AVPR2 vectors were constructed and transfection to HEK-293T cells. Immunofluorescence experiments were performed to investigate the expression and localization of the mutated protein and cAMP parameter assays were used to measure its activity in response to AVP.Results: The heights of the adult members affected with polyuria and polydipsia were normal, but all affected children had growth retardation. Next-generation sequencing identified a novel mutation in AVPR2 gene (c.530T > A) in this family. Bioinformatic analysis indicated that the mutation in AVPR2 changed the hydropathic characteristic of the protein and was probably deleterious. Although immunofluorescence showed that the mutated AVPR2 was normally expressed in the cell surface, the intracellular cAMP concentration stimulated by AVP was significantly lower in cells transfected with mutated AVPR2 than cells transfected with wild-type AVPR2. Based on the ACMG criteria, the novel c.530T > A variant of the AVPR2 gene was likely pathogenic and the affected family members were diagnosed as CNDI. After the confirmation of the diagnosis, the proband was treated with compound amiloride hydrochloride and rhGH, the symptoms of polyuria, polydipsia and growth retardation were all improved.Conclusion: These findings suggested that the novel mutation in AVPR2 (c.530T > A) was a true disease-causing variant with mild effects, which could be classified as a type III mutant receptor. Moreover, investigations of the function of growth hormone axis could be important for the pediatric CNDI patients with extreme short stature, and rhGH treatment might improve the final adult heights in these patients.

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Section: Discussionmentioning

confidence: 99%

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family

Guo

et al. 2021

Front. Pediatr.

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“…Different clinicians may suggest different treatments and diet plans for CNDI patients. Most clinicians (93%) prescribe thiazide for treating CNDI, whereas 62, 55, and 43% prescribe amiloride, non-steroidal anti-inflammatory drugs, and indomethacin, respectively, according to a survey (26). The most commonly used treatment regimen is hydrochlorothiazide (2-4 mg/kg/day) combined with indomethacin (0.75-1.2 mg/kg/day), which can effectively reduce urine volume and further reduce water excretion (27,28).…”

Section: Discussionmentioning

confidence: 99%

Case Report: A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr273Met Mutation in Arginine Vasopressin Receptor 2

Huang

et al. 2021

Front. Pediatr.

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Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary tubular dysfunction caused mainly by X-linked recessive inheritance of AVPR2 gene mutations. Pathogenic genes are a result of mutations in AVPR2 on chromosome Xq28 and in AQP2 on chromosome 12q13. The clinical manifestations of CNDI include polyuria, compensatory polydipsia, thirst, irritability, constipation, developmental delay, mental retardation, persistent decrease in the specific gravity of urine, dehydration, and electrolyte disorders (hypernatremia and hyperchloremia). Herein, we report a rare case of CNDI caused by an AVPR2 mutation in a 2-year-old Chinese boy who had sustained polyuria, polydipsia, and irritability for more than 20 months. Laboratory examinations showed no obvious abnormality in blood sodium and chloride levels but decreased urine osmolality and specific gravity. Imaging findings were also normal. However, genetic analysis revealed a C > T transition leading to T273M missense mutations in AVPR2. We provided the boy a low-sodium diet and administered oral hydrochlorothiazide and indomethacin for 1 month, after which his clinical symptoms significantly improved. This case report suggests that CNDI is characterized by pathogenic T273M missense mutations alone and expands our understanding of the pathogenesis of CNDI.

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“…Thus no specific prevention measures are available[ 13 ]. Currently, symptomatic treatments targeting clinical manifestations related to urine concentration dysfunction are mainly adopted, such as adequate water supplementation, low-sodium diets and oral medications, so as to achieve symptom relief, prevent dehydration and hypernatremia, improve the quality of life and prolong life expectation[ 14 ]. Commonly used drugs include hydrochlorothiazide, amiloride and indomethacin.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

et al. 2020

WJCC

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BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renal disorder that is caused by mutations in AVPR2 or aquaporin 2 ( AQP2 ). Up to now, there are few reports about CNDI in neonates. Early clinical manifestations of CNDI in neonates are atypical. A lack of understanding of the disease by clinicians causes frequent misdiagnoses or missed diagnoses, which may result in failure to administer treatments in time and ultimately leads to severe complications. In this study, clinical data of a case of AVPR2 gene mutation-induced CNDI, which was confirmed by genetic testing, were retrospectively analyzed 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 d period of pyrexia. The patient’s symptoms included recurrent pyrexia, hypernatremia and hyperchloremia, which were difficult to treat. The patient was fed on demand, and water was additionally provided between milk intakes. A combination 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 subsequently discharged. Genetic tests confirmed that the patient carried the AVPR2 gene missense mutation c.541C>T (P.R181C), and the patient’s mother carried a heterozygous mutation at the same locus. After clinical treatment with a combination of hydrochlorothiazide and amiloride, the body temperature and electrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth and development were observed. CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecific with some patients merely showing recurrent fever and electrolyte disturbance. Genetic testing of AVPR2 and AQP2 can be used for screening and genetic diagnosis of CNDI.

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A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr108Met Variant of Aquaporin 2

Cited by 4 publications

References 20 publications

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family

Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family

Case Report: A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr273Met Mutation in Arginine Vasopressin Receptor 2

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

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