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


CONCLUSIONS
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.
Abaci
Ayhan
A
Department of Pediatric Endocrinology, Dokuz Eylül Faculty of Medicine, Inciralti, Izmir, Turkey.
Wood
Kent
K
Demir
Korcan
K
Büyükgebiz
Atilla
A
Böber
Ece
E
Kopp
Peter
P
D000584:Amiloride / Q000627:therapeutic use; D002675:Child, Preschool; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D017483:Receptors, Vasopressin / Q000235:genetics*; D026941:Sodium Channel Blockers / Q000627:therapeutic use
D017483:Receptors, Vasopressin; D026941:Sodium Channel Blockers; D006852:Hydrochlorothiazide; D000584:Amiloride