title: Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients.
abstract: Congenital nephrogenic diabetes insipidus (NDI) is, in most instances, a rare X-linked recessive renal disorder (MIM 304800) characterized by the clinical symptoms of polyuria, polydipsia, and dehydration. The X-linked NDI is associated with mutations of the arginine vasopressin receptor type 2 (AVPR2) gene, which results in resistance to the antidiuretic action of arginine vasopressin (AVP) in the renal tubules and collecting ducts. Identification of mutations in the AVPR2 gene can facilitate early diagnosis of NDI, which can prevent serious complications such as growth retardation and mental retardation. We analyzed three unrelated Chinese NDI families and identified three mutations: R106C, F287L, and R337X. In addition, an A/G polymorphism at cDNA nucleotide position 927 (codon 309L) was identified. A functional expression assay of the R106C and F287L mutants in COS-7 cells revealed that both mutants show significant dysfunction and accumulate intracellular cyclic adenosine monophosphate in response to AVP hormone stimulation. These results facilitate the diagnosis of NDI at the molecular level in the Chinese population, and provide insight into the molecular pathology of NDI.
authors.affiliation: Department of Psychiatry, Tzu-Chi General Hospital and Tzu-Chi University, Hualien City, Taiwan.
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chen
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Liu
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
authors.forename: Ann-Ping
authors.initials: AP
authors.lastname: Tsou
authors.forename: Ching-Yuang
authors.initials: CY
authors.lastname: Lin
authors.forename: Ting
authors.initials: T
authors.lastname: Chao
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017483:Receptors, Vasopressin / Q000235:genetics*; D013624:Taiwan
chemical_list: D017483:Receptors, Vasopressin