title: Two novel mutations in seven Czech and Slovak kindreds with familial neurohypophyseal diabetes insipidus-benefit of genetic testing.
abstract: Familial neurohypophyseal diabetes insipidus (FNDI) is a rare hereditary disorder with unknown prevalence characterized by arginine-vasopressin hormone (AVP) deficiency resulting in polyuria and polydipsia from early childhood. We report the clinical manifestation and genetic test results in seven unrelated kindreds of Czech or Slovak origin with FNDI phenotype. The age of the sign outset ranged from 2 to 17 years with remarkable interfamilial and intrafamilial variability. Inconclusive result of the fluid deprivation test in three children aged 7 and 17 years old might cause misdiagnosis; however, the AVP gene analysis confirmed the FNDI. The seven families segregated together five different mutations, two of them were novel (c.164C > A, c.298G > C). In addition, DNA analysis proved mutation carrier status in one asymptomatic 1-year-old infant.
  
  
  CONCLUSIONS
  The present study together with previously published data identified 38 individuals with FNDI in the studied population of 16 million which predicts a disease prevalence of 1:450,000 for the Central European region. The paper underscores that diagnostic water deprivation test may be inconclusive in polyuric children with partial diabetes insipidus and points to the clinical importance and feasibility of molecular genetic testing for AVP gene mutations in the proband and her/his first degree relatives.
  
  
  BACKGROUND
  • At least 70 different mutations were reported to date in about 100 families with neurohypophyseal diabetes insipidus (FNDI), and new mutations appear sporadically. What is New: • Two novel mutations of the AVP gene are reported • The importance of molecular testing in children with polyuria and inconclusive water deprivation test is emphasized.
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrčková
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia.
authors.forename: Viktor
authors.initials: V
authors.lastname: Jankó
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Kytnarová
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Čižmárová
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Tesařová
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia.
authors.forename: Ľudmila
authors.initials: Ľ
authors.lastname: Košťálová
authors.affiliation: Department of Pediatrics, County Hospital Levice, SNP 19, 934 01, Levice, Slovakia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgová
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Dallos
authors.affiliation: 3rd Internal Clinic-Clinic of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Hána
authors.affiliation: Department of Pediatrics of the University Children's Hospital in Motol and 2nd Faculty of Medicine of Charles University in Prague, V Úvalu 84, 150 06, Prague 5, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Lebl
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Zeman
authors.affiliation: 2nd Department of Pediatrics, Faculty of Medicine, Comenius University in Bratislava and University Children's Hospital Bratislava, Limbová 1, 833 40, Bratislava, Slovakia. kovacsbox@gmail.com.
authors.forename: László
authors.initials: L
authors.lastname: Kovács
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001127:Arginine Vasopressin / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002648:Child; D018153:Czech Republic / Q000453:epidemiology; D020790:Diabetes Insipidus, Neurogenic / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059606:Polydipsia / Q000209:etiology; D011141:Polyuria / Q000209:etiology; D015995:Prevalence; D018154:Slovakia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001127:Arginine Vasopressin
keywords: AVP gene; FNDI; Mutation; Polyuria; Water deprivation test