A novel mutation in the AVPR2 gene (222delA) associated with X-linked nephrogenic diabetes insipidus in a boy with growth failure.

Abstract

OBJECTIVE:

To study the case of a 2 10/12-year-old boy who had growth failure and delayed bone maturation.

METHODS:

We reviewed the history, which revealed that he had had polyuria, polydipsia, lack of weight gain, and frequent vomiting since the age of 5 months. On physical examination, his height was 86 cm (-1.93 standard deviation [SD]), his weight 10.5 kg (-2.67 SD), and he had motor and mental retardation. His maternal great-grandfather also had polyuria and polydipsia (but not diabetes mellitus), suggesting X-linked nephrogenic diabetes insipidus as the underlying cause. The patient underwent a water deprivation-desmopressin test. The coding region of the AVPR2 gene was amplified by polymerase chain reaction and submitted to direct sequence analysis.

RESULTS:

The water deprivation test confirmed the diagnosis of diabetes insipidus, and administration of desmopressin did not diminish his water secretion. Direct sequencing of the AVPR2 gene revealed a novel deletion of adenine at position 222 (222delA) in exon 2. This mutation is predicted to lead to a frameshift beginning at amino acid 75 and a premature stop codon at position 115 (FS75>115X). His height and weight, as well as his motor skills, improved after initiation of therapy with hydrochlorothiazide and amiloride.

CONCLUSION:

Growth delay can be associated with diabetes insipidus. The X-linked nephrogenic diabetes insipidus in this boy is caused by a novel mutation in the AVPR2 gene that is predicted to truncate the receptor protein.

• Authors: Ayhan Abaci, Kent Wood, Korcan Demir, Atilla Büyükgebiz, Ece Böber, Peter Kopp
• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Endocr Pract) 2010 Mar-Apr Vol. 16 Issue 2 Pg. 231-6 ISSN: 1934-2403 [Electronic] United States
• PMID: 19703807 (Publication Type: Case Reports, Journal Article)

Chemical References

• Receptors, Vasopressin
• Sodium Channel Blockers
• Hydrochlorothiazide
• Amiloride

Topics

• Amiloride (therapeutic use)
• Child, Preschool
• Diabetes Insipidus, Nephrogenic (drug therapy, genetics)
• Genetic Diseases, X-Linked (drug therapy, genetics)
• Humans
• Hydrochlorothiazide (therapeutic use)
• Male
• Mutation
• Receptors, Vasopressin (genetics)
• Sodium Channel Blockers (therapeutic use)