Molecular basis of phenylketonuria and recombinant DNA strategies for its therapy.

Mutations in the human phenylalanine hydroxylase gene associated with two prevalent mutant alleles have been identified and shown to be in linkage disequilibrium with the corresponding mutant restriction fragment length polymorphism haplotypes. These results suggest the possibility of carrier detection in the population without a prior family history of phenylketonuria (PKU). Furthermore, recombinant retroviruses containing the full-length human phenylalanine hydroxylase cDNA have been constructed and used to transduce functional enzymatic activity into cultured hepatoma cells. Together with the recent success in retroviral infection of primary mouse hepatocytes, it will be possible to use the mouse model to investigate somatic gene therapy for PKU.