Association between minihaplotypes and mutations at the PAH locus in polish hyperphenylalaninemic patients

Hereditary hyperphenylalaninemia (HPA) is a disorder of amino acid metaboli sm and results from an insufficiency of hepatic phenylalanine hydroxylase ( PAH). HPA phenotypes form a spectrum ranging from classical phenylketonuria (PKU) to mild hyperphenylalaninemia (MHP). The phenotypic diversity reflec ts heterogeneity at the molecular level, and more than 320 different mutati ons in the PAH gene are known to date. The association of 3 mutations (R408 W, IVS10 and A403V) common in different European populations with a variabl e number tandem repeat (VNTR) and short tandem repeat sites (minihaplotype) in the PAH gene was examined in a group of Polish PKU and MHP patients. Ad ditionally, minihaplotypes were established for another 16 mutations. The p resented data support the hypothesis that the R408W/VNTR3/STR238 allele ori ginated among pre-Indo-Europeans on the territory in present-day Lithuania and Belarus. Mutation IVS10nt-11g-->a (IVS10) is strongly associated with V NTR7/STR250 minihaplotype and is possibly of Mediterranean origin. Copyrigh t (C) 2000 S. Karger AG, Basel.