Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel nonsense mutation in AVP-NPII gene.

Familial neurohypophyseal diabetes insipidus (FNDI) is a rare single-gene disorder caused by mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene. These changes impair the release of vasopressin from the posterior pituitary gland. In the present study, the AVP-NPII gene of a Chinese adult patient with central diabetes insipidus, the patient's symptomatic mother and an asymptomatic sister of the patient was sequenced. Examination of the family history revealed cases of FNDI across four generations. Gene sequencing analysis revealed a novel heterozygous mutation, c.268A>T (p.Lys90Ter), in exon 2 of the AVP-NPII gene, in the patient and the patient's mother, which led to the loss of 6 cysteine residues and aberrant disulfide bonds, which is predicted to alter the mature protein structure. The present study identified a novel heterozygous nonsense mutation of the AVP-NPII gene associated with FNDI, which broadens the spectrum of known mutations associated with this disorder and contributes to the understanding of its molecular basis.