Two Novel Aquaporin-2 Mutations in a Sporadic Japanese Patient with Autosomal Recessive Nephrogenic Diabetes Insipidus
| Title: | Two Novel Aquaporin-2 Mutations in a Sporadic Japanese Patient with Autosomal Recessive Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Tajima, Toshihiro; Okuhara, Kouji; Satoh, Kouhei; Nakae, Jun; Fujieda, MD, PhD, Kenji |
| Publisher: | Endocrine Journal |
| Date Published: | August 01, 2003 |
| Reference Number: | 635 |
We identified two novel mutations of the aquaporin-2 (AQP2) gene in a sporadic Japanese patient diagnosed with an autosomal recessive nephrogenic diabetes insipidus (NDI). The patient, a Japanese boy, was referred to our clinic at the age of 5 months because of unexplained recurrent fever. He was diagnosed with NDI by clinical, biochemical and endocrine findings. Molecular analysis demonstrated that he was a compound heterozygote for two mutations. One mutation consisted of a two base deletion in exon 1 (197, 198 delCA). This deletion caused a frameshift in the open reading frame, resulting in a premature stop codon 186 bases downstream in exon 1. The second mutation was a G to A transition of the terminal exon splice site (1502-1G-->A). To date, several mutations in the AQP2 gene have been described, however no splicing mutation in the AQP2 gene has been identified. The deletion mutation described in this case study was inherited paternally and the splicing site mutation was inherited maternally, indicating an autosomal recessive inheritance. In the present case study, we identified two new mutations in the AQP-2 gene. Previous studies have shown that there is no hot spot for mutations in the AQP-2 gene, and thus genetic analysis for individual patients is helpful for genetic counseling and early diagnosis.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The mutated AQP2 gene the boy inherited from his father consisted of a two base deletion in the first coding section of the gene. This resulted in a truncated AQP2 protein, one that does not achieve normal length. The mutated AQP2 gene he received from his mother occurred in the coding section responsible for the C-tail end of the AQP2 protein. This splicing mutation was the first splicing mutation found in an NDI related AQP2 mutation.
The 5 month old boy was treated with intravenous fluid administration and, later, hydrochlorothiazide. His NDI is considered under control.