title: Molecular analysis in familial neurohypophyseal diabetes insipidus: early diagnosis of an asymptomatic carrier.
abstract: Familial neurohypophyseal diabetes insipidus (FNDI) is an inherited deficiency of the hormone arginine vasopressin (AVP) and is transmitted as an autosomal dominant trait. In the present study we have analyzed the AVP-neurophysin II (AVP-NPII) gene in a Spanish kindred. Studies were performed on seven members (four clinically affected) of the family. Patients were diagnosed at the Hospital Universitario Gregorio Marañón (Madrid, Spain). The entire coding region of the AVP-NPII gene of all family members was amplified by PCR and sequenced. All affected individuals presented a missense mutation (G1757-->A) that replaces glycine at position 23 with arginine within the NPII domain. The substitution was confirmed by restriction endonuclease analysis and was present in heterozygosis. Additionally, one of the asymptomatic relatives (a girl 8 months old at the time of study) was identified as carrier of the same mutation and developed the disease 3 months later. The alteration found in the second exon of the gene in this family seems to be responsible for the disease, as all individuals harboring the mutation had been previously diagnosed or have eventually developed FNDI. Identification of the molecular defect underlying FNDI in affected families is a powerful tool for early asymptomatic diagnosis in infants.
authors.affiliation: Department of Endocrinology, Hospital de Cruces, Barakaldo, Basque Country, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Calvo
authors.forename: J R
authors.initials: JR
authors.lastname: Bilbao
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.forename: M D
authors.initials: MD
authors.lastname: Rodríguez-Arnao
authors.forename: L
authors.initials: L
authors.lastname: Castaño
mesh_terms: D001127:Arginine Vasopressin / Q000172:deficiency* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D003919:Diabetes Insipidus / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D009481:Neurophysins / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D009481:Neurophysins; D001127:Arginine Vasopressin; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases