Molecular analysis in familial neurohypophyseal diabetes insipidus: Early diagnosis of an asymptomatic carrier

Familial neurohypophyseal diabetes insipidus (FNDI) is an inherited deficie ncy of the hormone arginine vasopressin (AVP) and is transmitted as an auto somal dominant trait. In the present study we have analyzed the AVP-neuroph ysin II (AVP-NPII) gene in a Spanish kindred. Studies were performed on sev en members (four clinically affected) of the family. Patients were diagnose d at the Hospital Universitario Gregorio Maranon (Madrid, Spain). The entir e coding region of the AVP-NPII gene of all family members was amplified by PCR and sequenced. All affected individuals presented a missense mutation (G(1757)-->A) that replaces glycine at position 23 with arginine within the NPII domain. The substitution was confirmed by restriction endonuclease an alysis and was present in heterozygosis. Additionally, one of the asymptoma tic relatives (a girl 8 months old at the time of study) was identified as carrier of the same mutation and developed the disease 3 months later. The alteration found in the second exon of the gene in this family seems to be responsible for the disease, as all individuals harboring the mutation had been previously diagnosed or have eventually developed FNDI. Identification of the molecular defect underlying FNDI in affected families is a powerful tool for early asymptomatic diagnosis in infants.