OBJECTIVETo detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI).

METHODSClinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced.

RESULTSThe patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation.

CONCLUSIONThe congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Adolescent ; Base Sequence ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic ; congenital ; genetics ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: (70)Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and (187)Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, (70)Ala (GCC) to Asp (GAC) and (187)Arg (CGC) to His (CAC).
Aquaporin 2/*genetics ; Base Sequence ; Child, Preschool ; DNA/genetics ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic/congenital/*genetics ; Female ; Genes, Recessive ; Heterozygote ; Humans ; Infant ; Male ; Mutation, Missense ; Point Mutation ; Research Support, Non-U.S. Gov't