Nephrogenic syndrome of inappropriate antidiuresis.
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."
Feldman
Brian J
BJ
Department of Pediatrics, Division of Endocrinology, University of California at San Francisco, San Francisco, CA 94143, USA.
Rosenthal
Stephen M
SM
Vargas
Gabriel A
GA
Fenwick
Raymond G
RG
Huang
Eric A
EA
Matsuda-Abedini
Mina
M
Lustig
Robert H
RH
Mathias
Robert S
RS
Portale
Anthony A
AA
Miller
Walter L
WL
Gitelman
Stephen E
SE
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*
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin