Danish Center for Human Genome Research, John F. Kennedy Institute, Glostrup.
We present the results of a comprehensive study on the molecular basis of phenylketonuria (PKU) in Denmark. A strategy relying on PCR in combination with denaturing gradient gel electrophoresis for analyzing the coding sequence and splice site junctions of the phenylalanine hydroxylase gene allowed us to detect a molecular defect on 99% of 308 Danish PKU chromosomes. The mutational spectrum consists of 35 different mutations, including 23 missense mutations, 5 splice mutations, 4 nonsense mutations, and 3 deletions. Seventeen of these mutations have not been reported previously. The mutation detection assay presented in this report offers a simple and reliable methodological entity that can be applied to rapid diagnosis and carrier detection of phenylketonuria in any population, irrespective of the frequency and distribution of mutations.