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Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families.
J Pediatr Endocrinol Metab 2019; 32(8):915-920JP

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.

Authors+Show Affiliations

Department of Pathology, Chemical Pathology Laboratory, Queen Elizabeth Hospital, Room 817, 8/F, Block M, 30 Gascoigne Road, Kowloon, Hong Kong, Phone: +85252782423.Department of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong.Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.Department of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong.Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Pub Type(s)

Case Reports

Language

eng

PubMed ID

31271558

Citation

Leung, Mei Tik, et al. "Contiguous Gene Deletion in a Chinese Family With X-linked Nephrogenic Diabetes Insipidus: Challenges in Early Diagnosis and Implications for Affected Families." Journal of Pediatric Endocrinology & Metabolism : JPEM, vol. 32, no. 8, 2019, pp. 915-920.
Leung MT, Sit JKK, Cheung HN, et al. Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families. J Pediatr Endocrinol Metab. 2019;32(8):915-920.
Leung, M. T., Sit, J. K. K., Cheung, H. N., Iu, Y. P., Chan, W. K. Y., & Shek, C. C. (2019). Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families. Journal of Pediatric Endocrinology & Metabolism : JPEM, 32(8), pp. 915-920. doi:10.1515/jpem-2019-0028.
Leung MT, et al. Contiguous Gene Deletion in a Chinese Family With X-linked Nephrogenic Diabetes Insipidus: Challenges in Early Diagnosis and Implications for Affected Families. J Pediatr Endocrinol Metab. 2019 Aug 27;32(8):915-920. PubMed PMID: 31271558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families. AU - Leung,Mei Tik, AU - Sit,Jacqueline K K, AU - Cheung,Hoi Ning, AU - Iu,Yan Ping, AU - Chan,Winnie K Y, AU - Shek,Chi Chung, PY - 2019/01/15/received PY - 2019/05/16/accepted PY - 2019/7/5/pubmed PY - 2019/7/5/medline PY - 2019/7/5/entrez KW - ARHGAP4 KW - AVPR2 KW - X-linked KW - congenital nephrogenic diabetes insipidus KW - contiguous gene deletion SP - 915 EP - 920 JF - Journal of pediatric endocrinology & metabolism : JPEM JO - J. Pediatr. Endocrinol. Metab. VL - 32 IS - 8 N2 - 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. SN - 2191-0251 UR - https://www.unboundmedicine.com/medline/citation/31271558/Contiguous_gene_deletion_in_a_Chinese_family_with_X-linked_nephrogenic_diabetes_insipidus:_challenges_in_early_diagnosis_and_implications_for_affected_families L2 - https://www.degruyter.com/doi/10.1515/jpem-2019-0028 DB - PRIME DP - Unbound Medicine ER -