title: Association between minihaplotypes and mutations at the PAH locus in Polish hyperphenylalaninemic patients.
abstract: Hereditary hyperphenylalaninemia (HPA) is a disorder of amino acid metabolism 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 reflects heterogeneity at the molecular level, and more than 320 different mutations in the PAH gene are known to date. The association of 3 mutations (R408W, IVS10 and A403V) common in different European populations with a variable 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. Additionally, minihaplotypes were established for another 16 mutations. The presented data support the hypothesis that the R408W/VNTR3/STR238 allele originated among pre-Indo-Europeans on the territory in present-day Lithuania and Belarus. Mutation IVS10nt-11g-->a (IVS10) is strongly associated with VNTR7/STR250 minihaplotype and is possibly of Mediterranean origin.
authors.affiliation: Department of Medical Genetics, National Research Institute of Mother and Child, Warsaw, Poland. czarekz@imid.med.pl
authors.forename: C
authors.initials: C
authors.lastname: Zekanowski
authors.forename: M
authors.initials: M
authors.lastname: Jurkowska
authors.forename: J
authors.initials: J
authors.lastname: Bal
mesh_terms: D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D011044:Poland; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences
chemical_list: D010651:Phenylalanine Hydroxylase