Abstract
Familial neurohypophyseal diabetes insipidus is a rare genetic disease caused by AVP gene variants and is characterized by progressive polyuria and polydipsia in early childhood. Herein, we have reported the clinical symptoms and genetic test results of a Japanese patient with a family history of polyuria and polydipsia for over five generations. The proband was a 6-yr-old boy who was referred for the evaluation of polyuria and polydipsia. A hypertonic saline infusion test showed no increase in AVP levels and a water deprivation test followed by vasopressin administration confirmed the diagnosis of central diabetes insipidus. Genetic analyses of the patient and his affected mother revealed a novel heterozygous missense variant (c.308T>A, p.V103D). This variant was located in the region encoding the neurophysin II moiety. Computational analysis predicted that p.V103D is pathogenic, and a structural change was detected by viewing the three-dimensional structure of the protein model. To our knowledge, this is the first study to identify a novel missense variant, p.V103D, in a Japanese family with central diabetes insipidus. These findings expand the panel of AVP variants and facilitate the genetic diagnosis of familial neurohypophyseal diabetes insipidus.