Giuseppa Patti1, Saverio Scianguetta2, Domenico Roberti2, Alberto Di Mascio3, Antonio Balsamo4, Milena Brugnara5, Marco Cappa6, Maddalena Casale2, Paolo Cavarzere5, Sarah Cipriani7, Sabrina Corbetta8, Rossella Gaudino5, Lorenzo Iughetti9, Lucia Martini5, Flavia Napoli1, Alessandro Peri7, Maria Carolina Salerno10, Roberto Salerno11, Elena Passeri8, Mohamad Maghnie1, Silverio Perrotta2, Natascia Di Iorgi1. 1. Department of Pediatrics, IRCCS Istituto Giannina Gaslini Institute, University of Genova, Genova, Italy. 2. Department of Women, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli', Naples, Italy. 3. University of Trieste, Trieste, Italy. 4. Pediatrics Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy. 5. Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy. 6. Unit of Endocrinology, Bambino Gesù Children's Hospital, IRCCS, Roma, Italy. 7. Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Firenze, Ospedale Careggi Firenze, Firenze, Italy. 8. Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, University of Milan, Milan, Italy. 9. Policlinico Universitario Modena, Modena, Italy. 10. Department of Translational Medical Sciences-Pediatric Section, University of Naples Federico II, Naples, Italy. 11. SOD Endocrinologia, DAI Medico-Geriatrico, AOU Careggi Florence, Florence, Italy.
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) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two 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 the 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.
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) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two 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 the 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.