title: Genetic background of clinical homogeneity of phenylketonuria in Poland.
abstract: In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (< 1%), and G272ter (< 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań.
authors.forename: J
authors.initials: J
authors.lastname: Jaruzelska
authors.forename: R
authors.initials: R
authors.lastname: Matuszak
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: F
authors.initials: F
authors.lastname: Rey
authors.forename: J
authors.initials: J
authors.lastname: Rey
authors.forename: J
authors.initials: J
authors.lastname: Filipowicz
authors.forename: K
authors.initials: K
authors.lastname: Borski
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D001483:Base Sequence; D005820:Genetic Testing; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015345:Oligonucleotide Probes; D010651:Phenylalanine Hydroxylase