J Korean Med Sci.  2005 Dec;20(6):1076-1078. 10.3346/jkms.2005.20.6.1076.

Two Novel Mutations in the Aquaporin 2 Gene in a Girl with Congenital Nephrogenic Diabetes Insipidus

• Cheong HI
• Cho SJ
• Zheng SH
• Cho HY
• Ha IS
• Choi Y

• KMID: 2157767
• DOI: http://doi.org/10.3346/jkms.2005.20.6.1076

Abstract

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).

Keyword

Diabetes Insipidus, Nephrogenic; aquaporin 2; Mutation; NPA Motif

MeSH Terms

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

Figure

• 

  Fig. 1 (A) Direct sequence analysis at exon 1 and exon 3 of the aquaporin-2 genes originating from the patient, her mother and her father. The small squares indicate the sites of point mutation. (B) The pedigree showing autosomal recessive mode of inheritance.

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