Exon deletions of the PAH gene in Italian hyperphenylalaninemics

A consistent finding of many studies describing the spectrum of mutant phenylalanine hydroxylase alleles underlying hyperphenylalaninemia is the impossibility of achieving a 100% mutation ascertainment rate using conventional gene-scanning methods such as Denaturing Gradient Gel Electrophoresis (DGGE), Denaturing High Performance Liquid Chromatography (DHPLC), direct sequencing. In recent years, it has been shown that a significant proportion of these undetermined alleles consist of large deletions overlapping one or more exons. These deletions have been difficult to detect in compound heterozygotes by gene-scanning methods due to the masking effect by the non-deleted allele. To date no sys…