A Novel Mutation in the AVPR2 Gene in a Palestinian Family with Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus (NDI) is a clinical disorder characterized by a urinary concentrating defect resulting from resistance of the collecting duct to the antidiuretic action of vasopressin (AVP). X-linked NDI is the most common inherited form of NDI and is caused by mutations in the gene encoding the V2 vasopressin receptor (V2R).1,2 Mutations of AVPR2 are implicated in nearly 90% of all cases of congenital NDI.3 Affected males with X-linked NDI develop a renal concentrating defect which is unresponsive to desmopressin administration. These affected individuals usually present with symptoms of dehydration, hypernatremia, renal insufficiency, mental retardation, and failure to thrive (FTT). Heterozygous females exhibit variable degrees of polyuria and polydipsia due to skewed X-chromosome inactivation.4 Early recognition and treatment allow having a normal lifespan with appropriate physical and mental development.5 To date, 280 different mutations in the AVPR2 gene have been identified for V2R NDI, and the mutations spread throughout all portions of the protein.6