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 188
- Downloads 0
Vitamin D Deficiency and Insufficiency According to the Current Criteria for Children: Vitamin D Status of Elementary School Children in Turkey
Objective: This study aimed to determine the ratio of seasonal vitamin D deficiency and insufficiency in elementary school children aged between 6-9 years old, living in one of the largest metropols of Europe, İstanbul....
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...
A Mutation in INSR in a Child Presenting with Severe Acanthosis Nigricans
Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder due to mutations in the insulin receptor gene (INSR) which is mapped to 19p13.2. RMS is characterized by acanthosis nigricans, generalized lanugo, tooth...
Testicular Adrenal Rest Tumor in Two Brothers with a Novel Mutation in the 3-Beta-Hydroxysteroid Dehydrogenase-2 Gene
Testicular adrenal rest tumors (TART) occur frequently in adolescents and adults with 21-hydroxylase deficiency. There have been no reports of TART in children with 3β-hydroxysteroid dehydrogenase deficiency (HSD3β). Bio...
Effectiveness of Continuous Subcutaneous Insulin Infusion Pump Therapy During Five Years of Treatment on Metabolic Control in Children and Adolescents with Type 1 Diabetes Mellitus
Objective: To compare continuous subcutaneous insulin infusion (CSII) therapy with multiple daily insulin (MDI) therapy on metabolic control in children and adolescents with type 1 diabetes mellitus (T1DM) over the long...