A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus
Journal Title: Journal of Clinical Research in Pediatric Endocrinology - Year 2018, Vol 10, Issue 4
Abstract
Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the AVPR2 gene causing CNDI in a 6-year-old boy, presenting with growth failure and dull normal cognitive functions. Methods: The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day). The diagnosis of CNDI was established by a water-deprivation test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the AVPR2 gene for all participants were amplified and sequenced. Bioinformatics analysis for wild-type and mutant AVPR2 were obtained with Swiss-Model and UCSF Chimera 1.10.2. Results: A novel, hemizygous, missense mutation was identified at the position 80th in exon 2 (p.H80Y) of AVPR2 in the proband. The proband’s mother, maternal aunt and grandmother were heterozygous and his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure. Conclusion: p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant.
Authors and Affiliations
Aslı Çelebi Tayfur, Tuğçe Karaduman, Merve Özcan Türkmen, Dilara Şahin, Aysun Çaltık Yılmaz, Bahar Büyükkaragöz, Ayşe Derya Buluş, Hatice Mergen
Keywords
Related Articles
- EP ID EP420895
- DOI 10.4274/jcrpe.0097
- Views 171
- Downloads 0
Associations Between Serum Uric Acid Concentrations and Cardiometabolic Risk and Renal Injury in Obese and Overweight Children
Objective: The aim of this study was to assess the association between serum uric acid concentration (SUAC) and the parameters of the metabolic syndrome (MetS) and insulin resistance (IR). The secondary aim was to evalua...
A Child with Prostaglandin I2-associated Thyrotoxicosis: Case Report
Prostaglandin I2 (PGI2) causes hyperthyroidism, a critical complication in patients with pulmonary arterial hypertension (PAH). However, it remains unknown whether PGI2 may have unfavorable effects on thyroid function in...
A Case of the Perinatal Form Hypophosphatasia Caused by a Novel Large Duplication of the ALPL Gene and Report of One Year Follow-up with Enzyme Replacement Therapy
Hypophosphatasia (HPP) is a rare disease caused by mutations in the ALPL gene encoding tissue-non-specific isoenzyme of alkaline phosphatase (TNSALP). Duplications of the ALPL gene account for fewer than 1% of the mutati...
Erratum
Karti Ö. Letter to the Editor Regarding “Assessment of Retinal Nerve Fiber Layer Thickness in Non-Diabetic Obese Children and Adolescents”. J Clin Res Pediatr Endocrinol 2018;10:91-91. The second reference of the articl...
Transient Neonatal Diabetes due to a Mutation in KCNJ11 in a Child with Klinefelter Syndrome
Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with...