The aquaporin-2 water channel in autosomal dominant primary nocturnal enuresis.

Abstract

Nocturnal enuresis is one of the most common diagnoses in a pediatric clinic. Recently, linkage analysis revealed a 2-point lod score of 4.2 in 6 families with dominant primary nocturnal enuresis around the aquaporin-2 (AQP2) water channel locus. Since primary nocturnal enuresis is ameliorated by desmopressin, AQP2 expression is increased by desmopressin and AQP2 is essential for concentrating urine, we determined whether a mutation in the AQP2 gene could cause primary nocturnal enuresis in these families. Genomic DNAs of several patients from the 6 families were analyzed for disease causing mutations in the 4 exons of the AQP2 genes. In 1 family a G to A transition in the intron 1 splice donor site was found but it was also found in healthy subjects. In another family a C to T transition in the intron 1 splice acceptor region was identified but it was often found in splice acceptor sites. In 2 families a C to T transition was identified in the coding region of exon 3 but this mutation did not lead to a changed amino acid. Since no mutation in the AQP2 coding sequence was found, while this is essential for involvement in dominant primary nocturnal enuresis, the AQP2 gene is excluded as a candidate for autosomal dominant PNE in these families in which the disease co-segregates with chromosome 12q.