A methodological strategy for PAH genotyping in populations with a marked molecular heterogeneity of hyperphenylalaninemia

The elucidation of the molecular basis of hyperphenylalaninemia in various world populations (PKU Consortium Database: http://www.mcgill.ca/pahdb/) ha s revealed a remarkable molecular heterogeneity at the locus encoding for p henylalanine hydroxylase. As a consequence, genotyping of HPA patients has prompted the establishment of an impressive number of mutation detection pr otocols. In spite of the large variety of methods proposed so far, no compr ehensive strategy has been yet developed for the detection of PAH gene muta tions. Therefore, new approaches, combining the advantages of individual me thods are required, especially in populations with a high number of PAH gen e mutations. In this study, we propose the use of Reverse Dot Blot Analysis within a general mutation detection protocol to simplify the genotyping of hyperphenylalaninemics in the very heterogeneous population of Sicily (Ita ly). (C) 2001 Academic Press.