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


METHODS
Genomic DNAs of several patients from the 6 families were analyzed for disease causing mutations in the 4 exons of the AQP2 genes.


RESULTS
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.


CONCLUSIONS
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.
Deen
Peter M T
PM
Department of Cell Physiology, UMC St Radboud, Nijmegen, The Netherlands.
Dahl
Niklas
N
Caplan
Michael J
MJ
D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004252:DNA Mutational Analysis; D004775:Enuresis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010375:Pedigree
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins