THE GENETICS OF PRIMARY NOCTURNAL ENURESIS - INHERITANCE AND SUGGESTION OF A 2ND MAJOR GENE ON CHROMOSOME 12Q

Primary nocturnal enuresis (PNE), or bedwetting at night, affects appr oximately 10% of 6 year old children. Genetic components contribute to the pathogenesis and recently one locus was assigned to chromosome 13 q. We evaluated the genetic factors and the pattern of inheritance for PNE in 392 families. Dominant transmission was observed in 43% and an apparent recessive mode of inheritance was observed in 9% of the fami lies. Among the 392 probands the ratio of males to females was 3:1 ind icating sex linked or sex influenced factors. Linkage to candidate reg ions was tested in 16 larger families segregating for autosomal domina nt PNE. A gene for PNE was excluded from chromosome 13q in 11 families , whereas linkage to the interval D13S263-D13S291 was suggested (Zmax= 2.1) in three families. Further linkage analyses excluded about 1/3 of the genome at a 10 cM resolution except the region around D12S80 on c hromosome 12q that showed a positive two point lod score ill six of th e families (Zmax=4.2), This locus remains suggestive because the mater ial was not sufficiently large to give evidence for heterogeneity. Our pedigree analysis indicates that major genes are involved in a large proportion of PNE families and the linkage results suggest that such a gene is located on chromosome 12q.