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

2020; Oxford University Press; Volume: 105; Issue: 4 Linguagem: Inglês

10.1210/clinem/dgaa069

1945-7197

Alejandro García‐Castaño, Leire Madariaga, Gustavo Pérez de Nanclares, Amaia Vela, Itxaso Rica, Sonia Gaztambide, Rosa Martı́nez, Idoia Martinez de la Piscina, Inés Urrutia, Aníbal Aguayo, Olaia Velasco, Javier Eizaguirre, Maria Anton, Amparo Rodríguez, M. D. Rodríguez-Arnao, Cristina Luzuriaga, C Villabona, Francisco Eulógio Martinez, Concha Carles, Joaquín Ramírez, Fernando Paz Pellat, Francisco José, Pomares Gómez, M. Chueca, María del Carmen Temboury, María Pilar Bahillo, Luís Castaño,

Electrolyte and hormonal disorders

Abstract Context 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. Objective 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. Design The AVP-NPII gene was screened for mutations by PCR followed by direct Sanger sequencing in 15 different unrelated families from Spain. Results 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)). Conclusions 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.