Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene

Giuseppa Patti, Saverio Scianguetta, Domenico Roberti, Alberto Di Mascio, Antonio Balsamo, Milena Brugnara, Marco Cappa, Maddalena Casale, Paolo Cavarzere, Sarah Cipriani, Sabrina Corbetta, Rossella Gaudino, Lorenzo Iughetti, Lucia Martini, Flavia Napoli, Alessandro Peri, Mariacarolina Salerno, Roberto Salerno, Elena Passeri, Mohamad MaghnieSilverio Perrotta, Natascia Di Iorgi

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone.

AIM: To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus.

PATIENTS AND METHODS: We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating.

RESULTS: Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser), c.215 C>A (p.Ala72Glu) missense mutations and additional 8 different mutations previously described were identified; nine were missense and 1 non sense mutation. Most mutations (8 out of 10) occurred in the region encoding for the NPII moiety; 2 mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case.

CONCLUSION: adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.

Original languageEnglish
JournalEuropean Journal of Endocrinology
DOIs
Publication statusE-pub ahead of print - Jun 1 2019

Fingerprint

Dive into the research topics of 'Familial neurohypophyseal diabetes insipidus in 13 kindreds and 2 novel mutations in the vasopressin gene'. Together they form a unique fingerprint.

Cite this