CLINICAL PHENOTYPE OF NEPHROGENIC DIABETES-INSIPIDUS IN FEMALES HETEROZYGOUS FOR A VASOPRESSIN TYPE-2 RECEPTOR MUTATION

Nephrogenic diabetes insipidus (NDI) usually shows an X-linked recessi ve mode of inheritance caused by mutations in the vasopressin type 2 r eceptor gene (AVPR2). In the present study, three NDI families are des cribed in which females show clinical features resembling the phenotyp e in males. Maximal urine osmolality in three female patients did not exceed 200 mosmol/kg and the absence of extra-renal responses to 1-des amino-8-D-arginine vasopressin was demonstrated in two of them. All af fected females and two asymptomatic female family members were shown t o be heterozygous for an AVPR2 mutation. Skewed X-inactivation is the most likely explanation for the clinical manifestation of NDI in femal e carriers of an AVPR2 mutation. It is concluded that, in female NDI p atients, the possibility of heterozygosity for an AVPR2 gene mutation has to be considered in addition to homozygosity for mutations in the aquaporin 2 gene.