title: Nephrogenic syndrome of inappropriate antidiuresis.
abstract: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."
authors.affiliation: Department of Pediatrics, Division of Endocrinology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Feldman
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rosenthal
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Vargas
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Fenwick
authors.forename: Eric A
authors.initials: EA
authors.lastname: Huang
authors.forename: Mina
authors.initials: M
authors.lastname: Matsuda-Abedini
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lustig
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mathias
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Portale
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gitelman
mesh_terms: D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000097:blood*; D004252:DNA Mutational Analysis; D004231:Diuresis / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007010:Hyponatremia / Q000209:etiology; D007177:Inappropriate ADH Syndrome; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017483:Receptors, Vasopressin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012640:Seizures / Q000209:etiology; D014162:Transfection; D014556:Urine / Q000737:chemistry; D014883:Water-Electrolyte Imbalance / Q000150:complications / Q000235:genetics*
chemical_list: D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin