Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene

Abstract

Abstract. Congenital nephrogenic diabetes insipidus (CNDI)is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of 108 Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The 108 Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided.

A Case of Congenital Nephrogenic Diabetes Insipidus Caused by Thr108Met Variant of Aquaporin 2

“…In this study we reported a case of CNDI caused by a single nucleotide substitution (c.323C>T) in AQP2 gene leading to a missense variant (p.T108M) of AQP2. Notably, this same mutation was observed in a CNDI case that is, however, caused by a small deletion (127-128delCA)-triggered frameshift mutation forming a new stop codon at position 62, leading to the premature termination of AQP2 translation (12). This stop codon occurred prior to the c.323C>T mutation, therefore, whether or not the c.323C>T mutation had a significant role in that CNDI case remained unknown.…”

Severe congenital nephrogenic diabetes insipidus in a compound heterozygote with a new large deletion of the AQP2 gene. A case report

“…However, no gross deletion was found at this time so ever: a deletion of G at nucleotide 721 (721delG), a deletion of 10 nucleotides starting at nucleotide 763 (763_772del), and a deletion of 7 nucleotides starting at nucleotide 812 (812_818del) (Bichet et al, ; Kuwahara et al, ; Sohara et al, ). In addition, a study by Park, Baik, Cheong, and Kang, () described a young Korean male with a compound heterozygous mutations located in exon 1. One of the mutations was a frameshift mutation resulting from a deletion NM_000486.5:c.127_128delCA (p.Gln43Aspfs*63).…”

Nonobstructive Bilateral Hydronephrosis & Hydroureter from Nephrogenic Diabetes Insipidus with a Novel Mutation of AQP2 Gene (p.A123G)

“…CNDI is generally diagnosed in infantile stage. Typically, the infant developed intermittent fever and hypernatremia at one month of age 6,7) . However, this patient was mostly asymptomatic except for nocturia, and further evaluation was made only after an incidental finding of microscopic hematuria on annual health checkup.…”