HETEROGENEITY OF MUTATIONS IN BULGARIAN PHENYLKETONURIA HAPLOTYPE-1 AND HAPLOTYPE-4 ALLELES

A study of Bulgarian patients with classical PKU demonstrated that hap lotypes 1 and 4 carry a significant number of rare molecular defects r esulting from independent mutational events. Differences in mutations associated with these common haplotypes exist even between populations which share a common major PKU mutation. Some amino acid substitution s, previously reported to lead to mild phenylalanine hydroxylase defic iency, were detected in the present study in compound heterozygotes wi th severe PKU. These findings preclude carrier testing and hyperphenyl alaninemia typing by genomic analysis at least in the heterogeneous Bu lgarian population.