Advances in the diagnosis of phenylketonuria with the introduction of direct detection of PAH gene mutation

BACKGROUND: Phenylketonuria is as regards the genotype a very heterogenous disease. Successful prenatal and postnatal DNA diagnosis calls for knowledge of different mutations in a given population. The objective of the investigation was to introduce direct detection of 21 mutations in the gene for phenylalanine hydroxylase and to find the distribution and frequency of these mutations in the population of northern and southern Moravia. METHODS AND RESULTS: The authors analyzed a group of 95 patients where according to phenotypic classification classical phenylketonuria was involved which comprised 190 mutant alleles. The presence of mutations was assessed by means of a polymerase chain reaction of a Perkin Elmer DNA Thermal Cycler 480. From the total number of 21 mutations which were sought, 11 were identified in our population, which accounts for 80% of all mutations. It was revealed that mutation R408W is found in 55.3% of our patients. Twenty per cent of the mutations are still unknown. CONCLUSIONS: This investigation laid the foundations for direct DNA diagnosis of phenylketonuria in the Czech Republic. The results assembled in the Moravian region suggest that our population is as regards genotypes relatively homogenous. This gives great hope of successful prenatal diagnosis and postnatal genotype classification.