title: Novel mutation of aquaporin-2 gene in a patient with congenital nephrogenic diabetes insipidus.
abstract: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease, characterized by an inability of the kidney to concentrate urine in response to vasopressin. Three different inheritance patterns have been described, i.e., the X-linked recessive form associated with arginine vasopressin V2 receptor (AVPR2) gene mutations, the autosomal recessive and dominant forms of CNDI associated with mutations in the aquaporin-2 (AQP2) gene encoding the vasopressin-regulated water channel of the renal collecting duct. Our case is an 18-year-old male patient who complained of severe polyuria since his infancy. But his developmental and growth status were normal. He was diagnosed as CNDI by water deprivation test and genomic DNA sequencing, which revealed high plasma AVP levels but persistently low urine osmolalities to 6 h-water deprivation and the novel missense mutation S216F in exon4 of the AQP2 gene. Immunohistochemistry of renal biopsied tissue revealed that most of the AQP2 labeling was seen intracellularly in a dotted pattern in the collecting duct principal cells. Immunoblotting of urine samples revealed significantly decreased urinary excretion of AQP2 (approximately 7% of normal control). Here, we report a new case of CNDI associated with the novel missense mutation of the AQP2 gene.
authors.affiliation: Department of Endocrinology and Metabolism, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Moon
authors.forename: Han-Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yeon-Kyung
authors.initials: YK
authors.lastname: Choi
authors.forename: Hyun-Ae
authors.initials: HA
authors.lastname: Seo
authors.forename: Jae-Han
authors.initials: JH
authors.lastname: Jeon
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
authors.forename: Jung-Guk
authors.initials: JG
authors.lastname: Kim
authors.forename: Bo-Wan
authors.initials: BW
authors.lastname: Kim
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D051399:Aquaporin 2 / Q000235:genetics* / Q000652:urine; D001127:Arginine Vasopressin / Q000652:urine; D001483:Base Sequence; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense
chemical_list: D051399:Aquaporin 2; D001127:Arginine Vasopressin