B. Calvo et al., Molecular analysis in familial neurohypophyseal diabetes insipidus: Early diagnosis of an asymptomatic carrier, J CLIN END, 84(9), 1999, pp. 3351-3354
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.