Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study

Alejandro García Castaño, Gustavo Pérez de Nanclares, Leire Madariaga, Mireia Aguirre, Sara Chocron, Alvaro Madrid, Francisco Javier Lafita Tejedor, Mercedes Gil Campos, Jaime Sánchez del Pozo, Rafael Ruiz Cano, Mar Espino, Jose Maria Gomez Vida, Fernando Santos, Victor Manuel García Nieto, Reyner Loza, Luis Miguel Rodríguez, Emilia Hidalgo Barquero, Nikoleta Printza, Juan Antonio Camacho, Luis CastañoGema Ariceta, RenalTube Group

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15 Citations (Scopus)


© 2015, Springer-Verlag Berlin Heidelberg. Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height −1.9 ± 2.1 and Z-weight −2.4 ± 1.7), severe hypernatremia (mean ± SD; Na 150 ± 10 mEq/L), increased plasma osmolality (mean ± SD; 311 ± 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration. Conclusion: Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms.
Original languageEnglish
Pages (from-to)1373-1385
JournalEuropean Journal of Pediatrics
Issue number10
Publication statusPublished - 26 Oct 2015


  • AQP2
  • AVPR2
  • Heterozygous females
  • Nephrogenic diabetes insipidus


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