Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families
-
Mei Tik Leung
,
Jacqueline K.K. Sit
Abstract
Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.
Acknowledgments
We thank Mr. C.W. Cheng and Mr. C.C. Wu for their technical assistance.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Anesi L, de Gemmis P, Galla D, Hladnik U. Two new large deletions of the AVPR2 gene causing nephrogenic diabetes insipidus and a review of previously published deletions. Nephrol Dial Transplant 2012;27:3705–12.10.1093/ndt/gfs359Search in Google Scholar
2. Broides A, Ault BH, Arthus M-F, Bichet DG, Ellen Conley M. Severe combined immunodeficiency associated with nephrogenic diabetes insipidus and a deletion in the Xq28 region. Clin Immunol 2006;120:147–55.10.1016/j.clim.2006.05.001Search in Google Scholar
3. Demura M, Takeda Y, Yoneda T, Furukawa K, Usukura M, et al. Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus. Hum Mutat 2002;19:23–9.10.1002/humu.10011Search in Google Scholar
4. Dong Y, Sheng H, Chen X, Yin J, Su Q. Deletion of the V2 vasopressin receptor gene in two Chinese patients with nephrogenic diabetes insipidus. BMC Genet 2006;7:53.10.1186/1471-2156-7-53Search in Google Scholar
5. Fujimoto M, Imai K, Hirata K, Kashiwagi R, Morinishi Y, et al. Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes. BMC Med Genet 2008;9:42.10.1186/1471-2350-9-42Search in Google Scholar
6. Huang L, Li W, Tang W, Lu G. A novel AVPR2 missense mutation in a Chinese boy with severe inherited nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab 2011;24:807–9.10.1515/JPEM.2011.302Search in Google Scholar
7. Knops NB, Bos KK, Kerstjens M, van Dael K, Vos YJ. Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2. Am J Med Genet A 2008;146A:1853–8.10.1002/ajmg.a.32386Search in Google Scholar
8. Sasaki S, Chiga M, Kikuchi E, Rai T, Uchida S. Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clin Exp Nephrol 2013;17:338–44.10.1007/s10157-012-0726-zSearch in Google Scholar
9. Schoneberg T, Pasel K, von Baehr V, Schulz A, Volk HD, et al. Compound deletion of the rhoGAP C1 and V2 vasopressin receptor genes in a patient with nephrogenic diabetes insipidus. Hum Mutat 1999;14:163–74.10.1002/(SICI)1098-1004(1999)14:2<163::AID-HUMU8>3.0.CO;2-BSearch in Google Scholar
10. Schulz A, Sangkuhl K, Lennert T, Wigger M, Price DA, et al. Aminoglycoside pretreatment partially restores the function of truncated V(2) vasopressin receptors found in patients with nephrogenic diabetes insipidus. J Clin Endocrinol Metab 2002;87:5247–57.10.1210/jc.2002-020286Search in Google Scholar
11. Huang L, Poke G, Gecz J, Gibson K. A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability. Am J Med Genet A 2012;158A:2511–8.10.1002/ajmg.a.35591Search in Google Scholar PubMed
12. Tegay DH, Lane AH, Roohi J, Hatchwell E. Contiguous gene deletion involving L1CAM and AVPR2 causes X-linked hydrocephalus with nephrogenic diabetes insipidus. Am J Med Genet A 2007;143A:594–8.10.1002/ajmg.a.31536Search in Google Scholar PubMed
13. Bockenhauer D, Bichet DG. Nephrogenic diabetes insipidus. Curr Opin Pediatr 2017;29:199–205.10.1097/MOP.0000000000000473Search in Google Scholar PubMed
14. Carroll P, Al-Mojalli H, Al-Abbad A, Al-Hassoun I, Al-Hamed M, et al. Novel mutations underlying nephrogenic diabetes insipidus in Arab families. Genet Med 2006;8:443–7.10.1097/01.gim.0000223554.46981.7aSearch in Google Scholar PubMed
15. Kotnik P, Battelino T, Debeljak M, Podkrajsek KT, Waldhauser F, et al. Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab 2007;20:483–9.10.1515/JPEM.2007.20.4.483Search in Google Scholar PubMed
16. Cho SY, Law CY, Ng KL, Lam CW. Novel large deletion in AVPR2 gene causing copy number variation in a patient with X-linked nephrogenic diabetes insipidus. Clin Chim Acta 2016;455:84–6.10.1016/j.cca.2016.01.032Search in Google Scholar PubMed
©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Mini Review
- Endocrine manifestations of PHACE syndrome
- Original Articles
- Quantitation of the arginine family amino acids in the blood of full-term infants perinatally in relation to their birth weight
- Effect of supplementation with omega-3 fatty acids on hypertriglyceridemia in pediatric patients with obesity
- Pediatric diabetes inpatient care: can medical staff knowledge be improved?
- Association of lipid profile and BMI Z-score in southern Iranian children and adolescents
- Arterial stiffness in children and adolescents with and without continuous insulin infusion
- Fasting during the holy month of Ramadan among older children and adolescents with type 1 diabetes in Kuwait
- Evaluation of the relationship between short-term glycemic control and netrin-1, a urinary proximal tubular injury marker in children with type 1 diabetes
- Incidence of diabetic ketoacidosis in newly diagnosed type 1 diabetes children in western Saudi Arabia: 11-year experience
- Novel mutations and spectrum of the disease of NR0B1 (DAX1)-related adrenal insufficiency in Indian children
- Metabolic profile, cardiovascular risk factors and health-related quality of life in children, adolescents and young adults with congenital adrenal hyperplasia
- Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study
- Response to sapropterin hydrochloride (Kuvan®) in children with phenylketonuria (PKU): a clinical trial
- Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A in children: a single centre experience
- Benign thyroid nodules in pediatric patients: determining best practices for repeat ultrasound evaluations
- Letter to the Editor
- Thyroid function in males with fragile X syndrome
- Case Reports
- A case of a severe reaction following the use of bisphosphonates in a patient with osteogenesis imperfecta
- Cushing disease in a patient with nonbullous congenital ichthyosiform erythroderma: lessons in avoiding glucocorticoids in ichthyosis
- Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families
Articles in the same Issue
- Frontmatter
- Mini Review
- Endocrine manifestations of PHACE syndrome
- Original Articles
- Quantitation of the arginine family amino acids in the blood of full-term infants perinatally in relation to their birth weight
- Effect of supplementation with omega-3 fatty acids on hypertriglyceridemia in pediatric patients with obesity
- Pediatric diabetes inpatient care: can medical staff knowledge be improved?
- Association of lipid profile and BMI Z-score in southern Iranian children and adolescents
- Arterial stiffness in children and adolescents with and without continuous insulin infusion
- Fasting during the holy month of Ramadan among older children and adolescents with type 1 diabetes in Kuwait
- Evaluation of the relationship between short-term glycemic control and netrin-1, a urinary proximal tubular injury marker in children with type 1 diabetes
- Incidence of diabetic ketoacidosis in newly diagnosed type 1 diabetes children in western Saudi Arabia: 11-year experience
- Novel mutations and spectrum of the disease of NR0B1 (DAX1)-related adrenal insufficiency in Indian children
- Metabolic profile, cardiovascular risk factors and health-related quality of life in children, adolescents and young adults with congenital adrenal hyperplasia
- Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study
- Response to sapropterin hydrochloride (Kuvan®) in children with phenylketonuria (PKU): a clinical trial
- Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A in children: a single centre experience
- Benign thyroid nodules in pediatric patients: determining best practices for repeat ultrasound evaluations
- Letter to the Editor
- Thyroid function in males with fragile X syndrome
- Case Reports
- A case of a severe reaction following the use of bisphosphonates in a patient with osteogenesis imperfecta
- Cushing disease in a patient with nonbullous congenital ichthyosiform erythroderma: lessons in avoiding glucocorticoids in ichthyosis
- Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families
