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Utility of AVP gene testing in familial neurohypophyseal diabetes insipidus
Author(s) -
Chitturi Sridhar,
Harris Mark,
Thomsett Michael J.,
Bowling Francis,
McGown Ivan,
Cowley David,
Leong Gary M.,
Batch Jennifer,
Cotterill Andrew M.
Publication year - 2008
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03303.x
Subject(s) - diabetes insipidus , vasopressin , endocrinology , medicine , asymptomatic , mutation , gene mutation , gene , biology , genetics
Summary Context Familial neurohypophyseal diabetes insipidus (FNDI) is a rare disorder resulting from arginine vasopressin (AVP) gene mutations. A partial defect in AVP secretion occurs early in the course of FNDI and may not be detected by a water deprivation test (WDT). Testing for AVP gene mutations may confirm a diagnosis of FNDI when a WDT is inconclusive and may also predict individuals who will later develop FNDI. Objective To test the utility of AVP gene analysis in confirming the diagnosis of FNDI. Patients Five families (20 subjects, 14 symptomatic and six asymptomatic) with FNDI and nine children with idiopathic neurohypophyseal diabetes insipidus (INDI). Measurements Genomic DNA was analysed for AVP gene mutations using polymerase chain reaction (PCR) amplification and sequencing. Results Heterozygous AVP gene mutations were found in all subjects with FNDI but none of the ICDI patients. Each family had their own distinct mutation. We identified two novel mutations (C44W and C105S). One asymptomatic subject developed diabetes insipidus (DI) 4 months after detection of an AVP gene mutation. The WDT suggested partial DI in 4/6 but was normal in 2/6 children with FNDI. Conclusion AVP gene testing allowed diagnostic confirmation of FNDI when the WDT was inconclusive in symptomatic children, therefore obviating the need for a repeat WDT and enabling earlier initiation of appropriate treatment. AVP gene testing also has the potential to identify which asymptomatic children will later develop FNDI.