Forty-One Individuals With Mutations in the AVP-NPII Gene Associated With Familial Neurohypophyseal Diabetes Insipidus

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 4; pp. 1112 - 1118
• Main Authors: García-Castaño, Alejandro, Madariaga, Leire, Pérez de Nanclares, Gustavo, Vela, Amaia, Rica, Itxaso, Gaztambide, Sonia, Martínez, Rosa, Martinez de LaPiscina, Idoia, Urrutia, Inés, Aguayo, Anibal, Velasco, Olaia, Castaño, Luis
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-04-2020
• Subjects: Adolescent; Adult; Antidiuretics; Argipressin; Carrier proteins; Child; Child, Preschool; Cytotoxicity; Development and progression; Diabetes; Diabetes insipidus; Diabetes Insipidus, Neurogenic - genetics; Diabetes Insipidus, Neurogenic - pathology; Family; Female; Follow-Up Studies; Genetic aspects; Genetic Predisposition to Disease; Health aspects; Humans; Infant; Male; Middle Aged; Mutation; Neurophysin; Neurophysins - genetics; Physiological aspects; Pituitary (posterior); Polydipsia; Polyuria; Prognosis; Protein Precursors - genetics; Quality control; Rare diseases; Vasopressin; Vasopressins - genetics; Young Adult; Spain; AVP-NPII gene; familial neurohypophyseal diabetes insipidus
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa069

Familial neurohypophyseal diabetes insipidus is a rare disease produced by a deficiency in the secretion of antidiuretic hormone and is caused by mutations in the arginine vasopressin gene.
Clinical, biochemical, and genetic characterization of a group of patients clinically diagnosed with familial neurohypophyseal diabetes insipidus, 1 of the largest cohorts of patients with protein neurophysin II (AVP-NPII) gene alterations studied so far.
The AVP-NPII gene was screened for mutations by PCR followed by direct Sanger sequencing in 15 different unrelated families from Spain.
The 15 probands presented with polyuria and polydipsia as the most important symptoms at the time of diagnosis. In these patients, the disease was diagnosed at a median of 6 years of age. We observed 11 likely pathogenic variants. Importantly, 4 of the AVP-NPII variants were novel (p.(Tyr21Cys), p.(Gly45Ser), p.(Cys75Tyr), p.(Gly88Cys)).
Cytotoxicity seems to be due to consequences common to all the variants found in our cohort, which are not able to fold correctly and pass the quality control of the ER. In concordance, we found autosomal dominant familial neurohypophyseal diabetes insipidus in the 15 families studied.