Two novel mutations in the aquaporin 2 gene in a girl with congenital nephrogenic diabetes insipidus.
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: 70Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and 187Arg (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, 70Ala (GCC) to Asp (GAC) and 187Arg (CGC) to His (CAC).
Cheong
Hae Il
HI
Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. cheonghi@plaza.snu.ac.kr
Cho
Su Jin
SJ
Zheng
Shou Huan
SH
Cho
Hee Yeon
HY
Ha
Il Soo
IS
Choi
Yong
Y
D051399:Aquaporin 2 / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D018500:Diabetes Insipidus, Nephrogenic / Q000151:congenital / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D017354:Point Mutation
C496023:AQP2 protein, human; D051399:Aquaporin 2; D004247:DNA