title: Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene.
abstract: The aims of our research were to define the genotype-phenotype correlations of mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU) among the Israeli population. The mutation spectrum of the PAH gene in PKU patients in Israel is described, along with a discussion on genotype-phenotype correlations. By using polymerase chain reaction/denaturing high-performance liquid chromatography (PCR/dHPLC) and DNA sequencing, we screened all exons of the PAH gene in 180 unrelated patients with four different PKU phenotypes [classic PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia (MHP)]. In 63.2% of patient genotypes, the metabolic phenotype could be predicted, though evidence is also found for both phenotypic inconsistencies among subjects with more than one type of mutation in the PAH gene. Data analysis revealed that about 25% of patients could participate in the future in (6R)-L: -erythro-5, 6, 7, 8-tetrahydrobiopterin (BH4) treatment trials according to their mutation genotypes. This study enables us to construct a national database in Israel that will serve as a valuable tool for genetic counseling and a prognostic evaluation of future cases of PKU.
authors.affiliation: MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel. danib@migal.org.il.|Tel-Hai Academic College, Upper Galilee, Israel. danib@migal.org.il.
authors.forename: Dani
authors.initials: D
authors.lastname: Bercovich
authors.affiliation: MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.
authors.forename: Arava
authors.initials: A
authors.lastname: Elimelech
authors.affiliation: Department of Genetic Community, Public Health Services, Health Ministry and Hebrew University, Jerusalem, Israel.
authors.forename: Joel
authors.initials: J
authors.lastname: Zlotogora
authors.affiliation: MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.|Tel-Hai Academic College, Upper Galilee, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Korem
authors.affiliation: MIGAL, Galilee Technology Center, Human Molecular Genetics and Pharmacogenetics Laboratory, Kiryat Shmona, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Yardeni
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Gal
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Goldstein
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Bela
authors.initials: B
authors.lastname: Vilensky
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Segev
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Avraham
authors.affiliation: Tissue Typing Unit and Safra Children Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Loewenthal
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Gerard
authors.initials: G
authors.lastname: Schwartz
authors.affiliation: Metabolic Disease Unit, Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010649:Phenylalanine / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000235:genetics* / Q000502:physiology; D010661:Phenylketonurias / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase